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Review

MRI Evaluation of the Uterine Junctional Zone

1
Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2
Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
3
Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
*
Author to whom correspondence should be addressed.
Appl. Sci. 2021, 11(23), 11096; https://doi.org/10.3390/app112311096
Submission received: 5 October 2021 / Revised: 11 November 2021 / Accepted: 19 November 2021 / Published: 23 November 2021
(This article belongs to the Special Issue Recent Advances in Medical Imaging Technology)

Abstract

:
The identification of the junctional zone (JZ) of the uterus on magnetic resonance imaging (MRI) offers new opportunities and challenges for evaluating normal physiological changes and uterine pathologies. We reviewed common terminologies, physiologic changes, and relevant pathologies, with a focus on the measurement techniques and pitfalls in obtaining valid JZ metrics from MRI in humans. The purpose of this review is to provide background knowledge and practical information for measuring the JZ of the uterus on MRI. Recommendations for future work in this area are also discussed.

1. Introduction

Magnetic resonance imaging (MRI) has been used to evaluate uterine lesions since the 1980s. The advances in radiologic technology have allowed MRI of the pelvis to be completed within 30 min. The MRI signal characteristics of uterine tissues provide an excellent contrast between the endometrium, the uterine junctional zone (JZ), and the myometrium. Taking advantage of this excellent tissue contrast, the thickness and the diameter of the endometrium and myometrium can be evaluated in a superior way, compared to ultrasound (US) imaging.
This review provides an introduction to the identification of the JZ on MR imaging, a brief review of the physiological changes in the JZ, the effects of scanning orientations and time (age, menstrual cycle) on JZ measurements, a review of the controversies of the terminology of the JZ and the functional zone of the uterus, and recent observations on the accuracy and precision of the measurements. Due to the lack of established protocols and their pitfalls, the ability of MRI to differentiate between JZ abnormalities and pathologies is also addressed in this review. It is the authors¡¯ hope that this article will provide practical information for researchers and clinicians when interpreting MR images in research and in clinical settings.

2. Anatomy of the Uterus

The adult uterus is flattened in the anteroposterior dimension, resulting in a more triangular shape on the transverse images, in contrast to the round shape on the coronal images (Figure 1). In an adult, the normal uterus is about 7 cm in length, 4 cm in width, and 3 cm in depth. Anatomically, the uterus consists of the fundus, the uterine body, and the cervix. The endometrial layer from the fundus to the internal os of the cervix divides the uterine body into anterior and posterior myometrium. There have been various histological concepts regarding the myometrium. Since the 19th century, Goerttler made a dissection of the frozen uterine wall, which was first named in four layers: (i) a predominantly transverse outer layer, (ii) an intermediate layer with predominant circularly oriented muscle fibers, (iii) a plexus layer that contains vascular structures and multiple layers of muscle fibers, and (iv) a circular fiber layer of the internal os of the cervix (Figure 2) [1,2]. The traditional four-layer concept of the myometrium was often used in describing the architecture, but is probably not important clinically.
Curtis et al. first described the functional zone of the uterus as a hypoechoic layer adjacent to the endometrium on ultrasound images [3]. Later, this unique inner myometrial zone of the uterus was discovered on MRI, and the structure was named the JZ in 1987. The JZ and the functional zone of the uterus are often used interchangeably. Unlike the US, the JZ is not difficult to identify on MRI because of the excellent tissue contrast provided by a higher magnetic field at 1.5 Tesla or above. The exact anatomical function and clinical significance of the JZ is still under investigation. Despite all of the concerns, measurements derived from MR images have provided useful references in association with women¡¯s reproductive health and disease, which we will discuss in the sections that follow.

3. Identification of the JZ on MRI

In a normal, pre-menopausal woman at reproductive age, the T2-weighted (T2W) MR images clearly display the well-defined uterine zonal anatomy with (i) a thin, linear hyperintense signal of the endometrial cavity; (ii) an intermediate signal of the bright endometrium; (iii) a low signal intensity (SI) of the inner JZ at the inner third of the myometrium; and (iv) a more uniformly intermediate signal of the outer myometrium (Figure 3).
In addition to the unique characteristics on T2W images, the JZ can also be identified to a certain degree on T1-weighted (T1W) images, but this was rarely used for measuring its thickness. In contrast to the low SI of the JZ shown on T2W images, the JZ appears to have a lighter intensity (intermediate signal) than on T1W images. The hyposignal of the JZ, compared to the high-signal outer myometrium on T2W images, is thought to be mainly caused by tightly packed smooth muscle cells [4]. This smooth muscle layer at the JZ is often described as denser than the myometrium and is of greater importance for the contractile machinery of the uterus [5]. The plexus layer in the inner myometrium may be the JZ, containing multiple nerve bundles, blood vessels, and multiple layers of interdigitating muscle fibers that were well described in previous research [1,2]. Therefore, the intermediate signal of the JZ on T1W images is probably increased by more vascularity being contributed from the plexus layer, compared to that of the myometrium [1,2]. Due to the unique characteristics of the JZ on MRI, it is recognizable on T1W and T2W imaging; the JZ has been of significant interest in evaluating its roles in normal physiological conditions (such as the menstrual cycle and pregnancy) and in pathological conditions (such as dysmenorrhea, endometriosis, and infertility).

4. Terminology

In uterine MRI studies, inconsistent use of the terms of ¡°subendometrial¡±, ¡°functional zone¡±, ¡°junctional zone¡±, and ¡°inner myometrium¡± has been reported. The use of the term ¡°subendometrial¡± myometrium may assume a location between the endometrium and the JZ; however, the term ¡°subendometrial¡± is ambiguous on its own, and should be used carefully [6,7]. ¡°Functional zone¡± is also used to designate this low-intensity zone in sonographic work [8]. However, according to the MRCOG (Membership of the Royal College of Obstetricians and Gynecologists) standards, the term ¡°JZ¡± is recommended for structures identified on MRI [9]. For consistency, throughout this review, the term ¡°JZ¡± is used when referring to the structure of the low-intensity zone adjacent to the endometrium, or if the authors did not specifically indicate its detection via sonography or MRI.

5. MR Image Acquisition

Uterine anatomy and the spatial extent of lesions are usually examined using T2W MR images. The T2W images provide a good contrast between tissues. An intermediate T2W signal of the endometrium can be well differentiated from the hypointense signal of the JZ and the intermediate myometrium. To achieve clear definition of the zonal anatomy of the uterus, MRI protocols recommend using a higher field strength (3.0 Tesla) to acquire T2W images, which can provide a better signal-to-noise ratio, contrast, and spatial resolution than a 1.5 Tesla MRI machine [10,11]. The spatial resolution of pelvic MR images (including the uterus) should be, at a minimum, 3 mm slice thickness with 1¨C2 mm interslice gaps, pixel (matrix) sizes no greater than 1 mm, and a field of view less than 30 ¡Á 30 cm [9,12]. It is preferred to acquire MR images with a 3 mm slice thickness, no gap, and 1 ¡Á 1 mm pixel sizes, to provide an optimal resolution.
Although a routine MRI of the uterus is acquired with imaging planes in the orthogonal orientations (coronal, sagittal, or transverse) of the subject, the images do not always display uterine structures in the anatomical orientations (perpendicular or parallel to the long axis of the endometrium) of the JZ, due to its mobility and the oblique positions of the uterus. A sagittal or a transverse oblique view perpendicular to the endometrial canal, or a long axis/coronal oblique view parallel to the endometrial canal (double oblique) of the uterus, is recommended (Figure 4). These anatomical orientations aim to correct for uterine positions and provide accurate measurements based on this well-established approach [9,13]. Thus, the terms ¡°long-axis view¡±, ¡°coronal view¡±, ¡°coronal oblique view¡±, ¡°short-axis view¡±, ¡°transverse view¡±, ¡°transverse oblique view¡±, ¡°sagittal view¡±, and ¡°sagittal oblique view¡± are often used by different authors when referring to the planes of the same images that are perpendicular or parallel to the long-axis of the endometrial canal.

6. JZ Measurements

6.1. How to Determine the Position of the Thickness Measurements?

As was mentioned earlier, the anatomical long axis of the uterus must be determined prior to obtaining images. The challenge is that the long axis view (the uterus parallel to the superior¨Cinferior axis of the body, and the long axis of the endometrial canal) may not be the same as the coronal plane, which is parallel to the coronal plane of the body. Thus, the long axis view may be described in some studies as the coronal plane and/or in other studies as an oblique coronal plane. Similarly, the short-axis view (the transverse plane that is perpendicular to the uterine body or the long axis of the endometrial canal) may also be described as either the sagittal or the sagittal oblique plane. The difference between the ¡°imaging¡± plane (coronal, sagittal, or transverse) and the ¡°anatomical¡± plane (coronal oblique or sagittal oblique) becomes less obvious in retroverted/retroflexed and anteverted/anteflexed uterus cases (extreme posterior and anterior uterus tilt, respectively, where the angle of the endometrial axis nearly falls within the coronal or transverse plane of the body).
For consistency, we suggest defining the uterine body view according to its anatomical orientation (long axis, perpendicular/short axis, or other) with respect to the endometrial canal, regardless of the imaging plane, because MRI acquisitions may employ coronal, sagittal, or even oblique orientations. We recommend that any future methodological evaluation should include both dimensions/planes, in order to draw conclusions. For the remainder of this review article, we use the following terminology: images as parallel to the long axis of the endometrial canal are referred to as the long axis or the coronal plane, images as perpendicular to the long axis are referred to as the short axis, the transverse plane, or the sagittal plane, and both planes will be combined as any axis. The terms used for image acquisition or for defining the position in the previous studies are listed in Table 1, Table 2, Table 3, Table 4, Table 5 and Table 6.

6.2. JZ Appearance and Possible Delineation Sites

The appearance of the JZ is generally uninterrupted along the endometrium. However, previous studies have observed an interrupted appearance at the uterine corner (cornual) region of the JZ on the long axis/coronal images in approximately 33% of healthy volunteers [14]. On these images, JZ thickness measurements were acquired from an interrupted JZ layer at the fundus (Figure 5a,b) or were acquired from a continuous JZ layer (Figure 5c,d). Due to the lack of histology data, it is difficult to determine whether the interrupted appearance is the result of imaging acquisition/processing, such as the partial volume averaging of MRI or the presence of vessels in the JZ at this cornual region, or if the JZ is truly physiologically thinner at the cornual region. Either way, it is recommended that the JZ thickness measurements should be defined in a continuous, uninterrupted manner (Figure 5c,d). This recommendation is also suggested by the Morphological Uterus Sonographic Assessment (MUSA) group [7]. Depending on the measurement locations, there may be a difference in the JZ thickness between measurements acquired from the interrupted JZ and from the continuous JZ. Variations in the appearance of the JZ can be a potential source of variability and inconsistency in measurements.
The outer border of the JZ cannot always be easily identified, due to the gradual transition from the hypointense signal of the JZ to the intermediate signal of the outer myometrium (Figure 6a). In addition, the location of the inner border, outer border, and the maximum thickness of the JZ in each individual case could affect the variability of these measurements (Figure 6b). Although there are no detailed descriptions of the exact demarcation criteria for the outer border of the JZ in many studies [18,19,20,21,22,23], the SI profile of the pixel intensities (Figure 6a, top) illustrates different locations/positions for the outer border of the JZ based on the method used in the automated program JZtool [16], the ESHRE/ESGE 2013 consensus [6], or the MUSA group guidelines [24]. Given that different criteria for demarcation of the JZ border existed and the maximal thicknesses of JZ are measured on different image planes, it is important to interpret the consistency or variations of the JZ data by taking the image acquisition and the delineation methods into consideration, due to the unknown effects and interactions.
An anterior¨Cposterior (AP) JZ thickness ratio (also known as JZ differential) of a greater than two-fold difference between the anterior and the posterior uterus has been considered as suggestive of adenomyosis [25,26,27]. This ratio is independent of the absolute thickness of the JZ, and may not be affected by menstrual variations over the cycle. However, it is important to keep in mind that one must also interpret the AP JZ thickness ratio in accordance to different imaging planes and the regions of the uterus, where the thickness is measured. It is known that a higher maximal JZ thickness is located at the posterior wall of the uterus in the mid-sagittal images, which results in an AP JZ thickness ratio of 1.49 ¡À 0.48 in healthy pre-menopausal women [16]. This is probably why the interpretation criterion recommended by both the MUSA group [24] and the ESHRE/ESGE 2013 consensus [6] of the AP JZ thickness ratio varies, depending on the measuring planes (e.g., the mid-sagittal plane vs. the coronal plane).

6.3. How to Measure JZ Metrics?

With advancements in computing technology, JZ metrics are now measured by semi-automatic or automatic computer tools with graphical user interface rather than the traditional methodology of using calipers on physical films [6,16,28]. Several JZ metrics and ratios are derived from either the maximum thickness of the JZ (JZmax) or the mean thickness of the JZ (JZmean), or are assessed in combination with the myometrial thickness. JZmax is measured as the width between the borders perpendicular to the endometrium at the thickest part of JZ in the selected image plane. Most of the previous studies measured the JZmax from either the anterior or the posterior uterine wall. Similarly, JZmean is measured from either the anterior or the posterior uterine wall. The value is obtained from the mean of five repeated measurements of the maximum thickness along the same side of the anterior or the posterior uterine wall, respectively (Figure 7a), or from the mean of six thickness measurements of the length of the entire uterine endometrium (endometrium circumference) (Figure 7b) [6,17]. A statistical comparison across different studies was undertaken in this manuscript. In addition to the factors we mentioned, the mean JZ thickness, reported either from one side of the wall versus both sides, may be another potential source of variability in measuring the JZ [29].
There are many varieties of the JZ and the myometrium thickness measurements used in the literature and in clinical guidelines. These include (1) JZ maximum (maximum thickness in a single location); (2) JZ mean (mean of five JZmax per location); (3) JZ global (mean of six measurements along the endometrium circumference); (4) myometrial thickness (anterior and posterior thickness); (5) total uterine wall thickness (anterior and posterior total thickness); (6) AP JZ thickness ratio (JZ differential); (7) myometrial/JZ ratio; and (8) JZ/uterine thickness ratio. The illustrations are demonstrated in Figure 7a,b.

6.4. Physiologic Effects on JZ Measurements

The JZ undergoes dynamic changes in response to hormonal changes during the menstrual cycle and at different reproductive ages. Previous studies have observed that the thickness of the JZ increases with age [30,31]. In women over 35 years old with no parity, JZ thickness reaches its maximum, then decreases gradually after 40 years of age [32]. In general, the JZ is described as having a low signal intensity on T2W images during the first decade of the reproductive age. This is consistent with a compactly arranged and predominantly circular smooth muscle layer structure. Later in the fourth decade, the JZ becomes less distinguishable from the myometrium, which is thought to be the result of a gradual diminishment in the differences of the hormonal receptors [33].
During the menstrual cycle, the JZ of premenopausal women varies in thickness, depending on the phase of the cycle [34]. The normal cyclic fluctuation is regulated by ovarian hormones (estrogen and progesterone). Therefore, the normal uterus does not only differentiate from hyper-/hypoestrogenism at different phases of the menstrual cycle, but it is also likely influenced differently in women of different reproductive ages [15]. Overall, the thickness of the JZ could be influenced by hormonal differences due to different reproductive ages and the phases of the menstrual cycle. At the same time, the use of hormonal contraceptives could also suppress the fluctuation of the JZ thickness, causing either thinner or thicker measurements, depending on the dosage and type of contraceptives [34].

6.5. Variations in Anatomical and Pathological JZ Measurements

As we previously mentioned, the outer myometrium can be divided into an anterior portion and a posterior portion by the endometrial cavity. Thus, the thickness of the JZ can be measured separately from the anterior wall (JZant) and the posterior wall (JZpos) along the circumference of the endometrial canal. To review the current measurement strategies for JZ thickness described in clinical guidelines [6,24] and a few exemplary research papers (either an accurate or a precise analysis on JZ metrics), summary tables for the two groups are provided in this review (Table 1, Table 2, Table 3, Table 4, Table 5 and Table 6). We set the criteria as follows: (1) studies must have been published using reproducible methods of JZ measurement on MRI; and (2) they must have used a consistent terminology to describe the imaging acquisition plane and the measuring sites. In addition to the methodological considerations, there are physiological influences of the scanning age and of the menstrual cycle (or other hormonal states) that were described in the literature. Therefore, Tables are provided as a summary of the literature data regarding clinical guideline reviews (Table 1) and of research studies that present data on either health or disease conditions (Table 2, Table 3, Table 4, Table 5 and Table 6). The parameters are (1) the age of the scan, (2) the hormonal level (cycle phase and hormonal replacement), (3) the imaging plane used, (4) what variables are measured, (5) the location of the measurements, and (6) the thresholds for pathological classification. As described above, JZ metrics were measured at different positions (imaging plane) and on different sites of the endometrium circumference (anterior, posterior, lateral, etc.), which we have compiled in the tables.
To our knowledge, only a few research studies evaluate and address the accuracy and precision of measurement in association to different locations or positions of the uterus [14,15,16,17,18]. Thus, the majority of literature data are from those research studies that are not involved in the evaluation and address of accuracy and precision of measurements. These data are less systematically collected and organized than data from methodological evaluation studies. The following six tables have been generated to show factors that may be associated with the accuracy and precision of the JZ measurements. Table 1 lists the thresholds and the terminologies of locations used in clinical recommendations and clinical guidelines. Table 2 lists JZ measurements from studies that present the methodology evaluation. The average age and the distribution with the standard deviation (SD) are shown in years. If the numbers are not shown in Table 2, it means that either the data were not measured from the particular site and the plane (indicated with ¡°¨C¡±), or the data are available but were not presented by the authors (indicated with ¡°/¡±). The terms used for image acquisition and the orientations defined in the original article are listed below, in the column heading of each parameter. The summary data on JZ measurements in the general population (Table 3), in healthy subjects (Table 4), in adenomyosis patients (Table 5), and in patients with infertility, endometriosis, or other conditions (Table 6), from past studies, are provided similarly to Table 2, based on the information provided by the authors. Table 3 and Table 4 include the measurements of healthy cases, while Table 3 also includes a small number of cases which have a small lesion that does not meet the current diagnostic criteria for adenomyosis. Table 5 and Table 6 include the measurements of abnormal cases. The abbreviations used for a number of commonly measured and derived variables are defined in Table 2. Studies that do not apply reproducible measurement methods are not listed.
In some of the previous studies, only one side of the anterior or the posterior wall is examined during the JZ thickness measurements due to local lesions (e.g., adenomyosis or leiomyomas). In these cases, only the unaffected side is measured to represent the ¡°healthy¡± reference. This measurement approach (using the unaffected side of an anteroposterior thickness) provides useful clinical information [21,35,36,37]; however, this type of approach may be biased for characterization. In our opinion, the current lack of normal reference data with accurate and reproducible methods, from which the reference range of normal or abnormal cases can be defined and established, is probably one of the factors that results in the variability and differences in the diagnosis on JZ-related pathologies. It is our belief that there would be a great clinical value to measuring the JZ thickness globally (along the entire endometrial circumference) to establish normative reference values for objective evaluation. This is similar to the approach we proposed for a systematic measurement of the endometrium described elsewhere [28].
We are aware of some limitations due to the inconsistent use of terms, both of the location and of the imaging plane. Therefore, we organized the literature data according to the terms and the descriptions used by individual authors. We have listed all of the descriptors used in past studies that are analogous to the short-axis images in a column together. Similarly, we have listed all of the descriptors used in past studies that are analogous to the long-axis images in one column. We have arranged these six summary tables for the aims of providing a straightforward reading of information needed for evaluating the JZ measurements. As a result, a high degree of data loss is noticed from the information in the papers listed in Table 3, Table 4, Table 5 and Table 6, due to the lack of details, clear descriptions, or a consistent measuring method.

7. The Relationship of the JZ Metrics and the Pathologies

Adenomyosis is a benign disease characterized by the presence of endometrium-like glands and stroma within the myometrium with uterine wall hypertrophy and muscular hyperplasia. It is a common condition related to infertility, chronic pelvic pain, and excessive menstrual bleeding (dysmenorrhea) [52,53]. Clinically, transvaginal ultrasound is often used as a first-line imaging exam when adenomyosis is suspected. The sonographic diagnostic features of adenomyosis include asymmetric thickness of the myometrium, cystic anechoic spaces, or hyperechoic islands or linear striations in the myometrium, caused by the presence of ectopic endometrial tissues within the uterine muscularis [54]. Although transvaginal ultrasound has its advantages, such as availability, relatively low cost, and ease of use, MRI is superior in confirming a diagnosis of adenomyosis and in excluding other pathologies [55]. The presence of high SI foci in the JZ and myometrium on T2W or T1W MR images has been consistently proposed as one of the hallmark features of adenomyosis [56]. However, some other indicators, such as poor definition of the endometrial¨Cmyometrial border, are less consistent.
As early as 1990, Mark et al. described that if the JZmax was equal to or greater than 12 mm, there would be a 100% predictive value of adenomyosis. If the JZmax was smaller than 8 mm, the predictive value of adenomyosis would be absent, and the diagnosis was excluded. However, adenomyosis did not appear to have any correlation with the JZ thickness when the JZmax was between 8 mm and 12 mm [20]. Nevertheless, previous studies based on smaller sample sizes (n < 50) have shown inconsistent sensitivities and specificities for a JZmax threshold of 12 mm to predict adenomyosis [9].
In 2009, Bazot et al. demonstrated inconsistent results in a large study (n = 131) with a broad range of ages (18 to 68 years) that a JZmax of equal to or greater than 12 mm was a 63% predictive value for adenomyosis, with a 97% specificity and a 41% sensitivity [36]. Later, in 2012, Bazot et al. conducted another large study (n = 206) with patients of a younger age (18 to 53 years), aiming to find out the optimal cutoff to assess the diagnostic value of the JZmax measurements [22]. In this study, the cutoff of the JZ thickness in diagnosing adenomyosis was evaluated with two groups: one was to include all cases (both leiomyomas and without leiomyomas), and the other was to include only cases without leiomyomas. The result of the optimal cutoff of the JZmax suggested that 12 mm was not an optimal cut off; instead, 10 mm provided a better diagnostic accuracy (81%) for adenomyosis (although they stated that regardless of the presence of leiomyomas, the JZmax equal to or greater than 10 mm indicates a sensitivity and specificity between 84¨C85% and 75¨C77%, respectively).
As mentioned previously, many factors may alter the thickness of the JZ in a normal uterus; these include reproductive age, cycle phase, and the use of hormone therapy. At this time, no study has addressed the interaction of all of these factors simultaneously using JZ measurements. Even though it is common to measure the JZmax on all of the uterine walls or positions in clinical scenarios, diagnostic criteria have not yet adopted a position-specific threshold or an age/cycle-specific threshold, when the JZmax is measured [27,36,43]. To account for the physiologic variations in the JZ thickness, a myometrial/JZ thickness ratio or an AP JZ thickness ratio (JZ differential) is often used in the clinic to help identify abnormality.
The myometrial/JZ thickness ratio (myometrial thickness divided by JZ thickness) was first proposed by Hricak et al. in 1983 [4]. An abnormal myometrial/JZ thickness ratio of equal to or greater than 4, measured from the sagittal plane at mid-line, would yield a 100% accuracy in diagnosing adenomyosis. In 2001, Novellas et al. reported a 98% specificity and 97% sensitivity in diagnosing adenomyosis when the myometrial/JZ thickness ratio was equal to or less than 2.2 [43]. Their method, however, employed a measurement of the anterior and the posterior walls of the uterus, separately, in the long-axis images.
The AP JZ thickness ratio (the JZ differential) was first proposed by Mark et al. [20]. The criterion of the AP JZ thickness ratio at 1.83 or greater provides a 91% specificity and 87% sensitivity in the diagnosis of adenomyosis [36]. An alternative threshold of 1.5 has also been suggested for adenomyosis, which demonstrates a high inter-observer agreement with a good specificity and negative predictive value, but with a lower sensitivity and positive predictive value in the diagnosis [57,58]. The more recent MUSA group proposed a JZmax threshold of 12 mm for the diagnosis of adenomyosis in the sagittal plane, while a JZ differential of 5 mm (i.e., [JZmax,ant ? JZmax,pos] ? 5 mm, or vice versa) can be found in the coronal plane [7,24]. This update may help clinical radiologists and sonographers with a clearer description and criterion when reporting ultrasound images. However, the diagnostic criteria of 12 mm in the sagittal plane and an JZ differential of 5 mm in the coronal plane are not directly comparable, due to the difference in imaging planes, and thus represent differences in the anatomical locations. It is important to note this difference when applying the criteria in different orientations.
Although numerous studies of the JZ characteristics have been proposed and adopted clinically, for now, the criteria that were recently recommended by the ESHRE/ESGE consensus [6] and the MUSA group [7] are different: (1) the JZmax equal to or greater than 12 mm when the measurement location is not specified (i.e., at any location); (2) the JZ differential (AP JZ thickness ratio) of at least a two-fold difference between the anterior and the posterior uterine walls; and (3) the abnormal myometrial/JZ thickness ratio. A similar, but more relaxed criterion for adenomyosis based on MRI was proposed by the ESHRE/ESGE consensus [6], such that if the case shows a low SI thickening of the JZ with a JZ/total uterine wall ratio greater than 40% on T2W images, the woman is likely to have diffuse adenomyosis.

8. The Accuracy and Precision in Estimating the JZ Metrics in Different Planes

Methodological papers that describe the measurement reliability from reproducibility studies under similar conditions (the repeatability that is measured by the same or different observers for the same cases for a given measuring technique) and under different conditions (the reproducibility measured by different observers for a given measuring technique), are limited in this field [59].
As of 2011, Champaneria et al. claimed that a low quality of evidence and a risk of bias for interpreting the JZ thickness as a diagnostic criterion of adenomyosis existed, due to the fact that some important information regarding the image acquisition and the measurement locations in the past research studies were often unavailable in the articles [9,12]. Without clear indications and descriptions in these studies, the measurement interpretation could be inconsistent and variable.
An MRI of the pelvis often acquires images in three orthogonal orientations (coronal, transverse, and sagittal) (Figure 1). However, the oblique positions of the uterus often do not fall within the orthogonal planes of the pelvis. Therefore, oblique images that are perpendicular or parallel to the long axis of the uterus (e.g., the endometrial canal) at different locations (e.g., the anterior or the posterior wall) should be acquired, measured, and validated. Recent methodological studies have demonstrated that JZ metrics are influenced by the imaging plane. For example, the posterior JZ thickness is greater than the anterior JZ thickness when measured in the transverse plane; however, the opposite is true in the sagittal plane [15,16,60]. There are no significant differences found in the anterior and the posterior JZ thickness measured in the coronal plane [16].
A study based on healthy volunteers (n = 5, age 24.6 ¡À 3.2 years) observed a high variability when measurements were averaged from all of the locations and planes by the same observer (mean ¡À SD = 7.9 ¡À 1.8 mm); among the sites of the anterior and the posterior wall, the maximum differences were found to be 5 mm at the cornual region in the long axis images [14]. The variability was significantly decreased by 37% if the measurements were limited to the body of the uterus in the short axis images (mean ¡À SD = 5.0 ¡À 1.1 mm), compared to the body and the cornual region in the long-axis images (mean ¡À SD = 8.0 ¡À 2.1 mm) [14]. For a given location at the posterior wall, an earlier methodological study of healthy volunteers (n = 10, age 24.9 ¡À 2.4 years) demonstrated that the JZmax had the highest inter-observer agreement and consistency (mean = 9.0 ¡À 2.0 mm, with a 0.96 intraclass correlation coefficient (ICC)) and the lowest overall relative variability (the coefficient of variation 0.8) in the measurements of the JZmax, as well as in the mean JZ thickness at the fundus for the posterior uterine wall [16]. The myometrial/JZ thickness ratio on the posterior uterine wall, measured at the mid-sagittal image, also had a high inter-observer agreement, with an ICC of 0.817.
When the images are parallel to the long axis of the endometrial cavity, the visualization of the JZ may be partially excluded from the single-slice acquisition, especially in cases with extreme flexed uterine positions. Due to the curved shape of the long-axis view of the uterine body on the single slice, the measured JZ metrics in this orientation may represent a partial endometrium circumference, rather than an adequate sample from a global measurement along the entire endometrial circumference of 360 degrees. In addition, due to a broader anterior/posterior uterine wall in the coronal plane, compared to the thickness of the walls in the sagittal plane, the SI transition of the JZ to the myometrium in the coronal plane is less clear in a narrow, hypointense JZ (Figure 6). This difference may have an impact on the measurement precision when different planes are used. It is likely that the precision derived from the same observer or from multiple observers may not be interchangeable, due to low precision and subjective criteria between one method and another, or between one plane and another.
Table 2. Summary of methodology evaluation in JZ measurement. Most of the method (MRI protocol) are based on T2WI. If the method is based on T1WI, it is addressed in the table. JZ thickness in millimeters (mean ¡À standard deviation (SD)) measured from anterior uterine wall (ant) or posterior uterine wall (pos) in short axis (sagittal plane) or long axis (coronal plane). Age in years (mean ¡À SD) and hormonal effect are addressed in the table when data are available. ¡°?¡± = unavailable data or descriptive data; ¡°/¡± = data available but not presented by the authors; ¡°¨C¡± = measurement does not done from this parameter.
Table 2. Summary of methodology evaluation in JZ measurement. Most of the method (MRI protocol) are based on T2WI. If the method is based on T1WI, it is addressed in the table. JZ thickness in millimeters (mean ¡À standard deviation (SD)) measured from anterior uterine wall (ant) or posterior uterine wall (pos) in short axis (sagittal plane) or long axis (coronal plane). Age in years (mean ¡À SD) and hormonal effect are addressed in the table when data are available. ¡°?¡± = unavailable data or descriptive data; ¡°/¡± = data available but not presented by the authors; ¡°¨C¡± = measurement does not done from this parameter.
Authors (Year)/No. of Cases/Age (Reproductive Age and Cycle Day, Use of Hormonal Drugs)Measured Sites/Position (from SA or LA)JZ Metrics
JZmaxJZmeanJZ Global Max 1JZ Global Mean 2JZ Global Mean *,3Myometrium ThicknessAP JZ Thickness Ratio (JZ Differen-tial)Myome-trium/JZ Ratio 4JZ/Total Uterine Thickness (JZ Ratio) 5
Lin et al. (2013) [17]/n = 10/age 24.9 ¡À 2.4/proliferative
phase/NA
ant (mid-sagittal)5.6 ¡À 1.6 mm6.1 ¡À 1.3 mm——–
ant (mid-coronal)5.5 ¡À 1.5 mm6.2 ¡À 1.0 mm——–
pos (mid-sagittal)9.0 ¡À 2.0 mm7.7 ¡À 1.3 mm——–
pos (mid-coronal)6.0 ¡À 1.8 mm6.4 ¡À 1.2 mm——–
Gordts et al. (2015) [18]/n = 72/age 23¨C51/day 8¨C12/NAPosterolateral quadrant; (SA/transverse)¡ª5.7 ¡À 1.4 mm——
Bhagavath et al. (2017)/n = 28/age 26¨C43/?/NAant and pos (any axis)6.1 ¡À 1.4 mm–6.3 ¡À 1.1 mm—0.25¨C0.32 *****-
Nougaret et al. (2017) [16]/n = 19/age 37 ¡À 7/day 7¨C22/NA (T1WI)ant (mid-sagittal, fundus) 6.5 ¡À 1.8 mm6.6 ¡À 1.4 mm——
ant (mid-sagittal, body)6.3 ¡À 1.5 mm6.3 ¡À 1.5 mm——
pos (mid-sagittal, fundus)8.6 ¡À 1.8 mm7.4 ¡À 1.7 mm—10.6 ¡À 2.6 mm-1.5 ¡À 0.4-
pos (mid-sagittal, body)8.1 ¡À 1.6 mm7.4 ¡À 1.4 mm——–
/ (mid-sagittal, anterior and posterior wall)——1.3 ¡À 0.2–
Nougaret et al. (2019)/n = 60/age 28¨C41/day 7¨C22/NA (T1WI)ant (mid-sagittal)6.6 ¡À 1.3 mm——–
pos (mid-sagittal)9.0 ¡À 2.0 mm——–
/ (mid-sagittal, anterior and posterior wall)——1.4 ¡À 0.2–
Lind et al. (2020) [15]/n = 135/age 32 ¡À 5/proliferative phase/57% using hormonal drugsant (mid-sagittal)7.8 ¡À 1.8 mm——1.3 ¡À 0.4-
ant (mid-coronal)7.4 ¡À 1.8 mm——1.0 ¡À 0.2-
pos (mid-sagittal)5.8 ¡À 1.6 mm——–
pos (mid-coronal)7.3 ¡À 1.8 mm——–
Metric Terminology:
JZmax = Abbreviation of JZ thickness (maximum). It is equivalent to the terminology of ¡°maximal JZ thickness¡± used in ESHRE/ESGE Consensus [6] and the MUSA group guidelines [24]. JZmax is defined as the width between the JZ¡¯s borders perpendicular to the endometrium at the thickest part of the JZ layer in the selected image plane.
JZmean = Abbreviation of JZ thickness (mean). It is equivalent to the terminology of ¡°mean JZ thickness¡± used in ESHRE/ESGE Consensus [6] and the MUSA group guidelines [24]. JZmean is defined as the mean of five JZmax at equal space within 2 cm of the uterine body along the same side of the anterior or posterior uterine wall (Figure 7a) [17].
1 JZ global max = Abbreviation of JZ global thickness (max). It is adopted from Bhagavath et al. 2017, which the measurement is based on JZ metrics automated derived from the entire uterine body using multiatlas labeling method from all the three orthogonal imaging orientations. JZ global max is defined as a pixel that has the highest intensity in the global JZ.
2 JZ global mean = Abbreviation of JZ global mean thickness. It is adopted from Bhagavath et al. 2017, which the measurement is based on JZ metrics automated derived from the entire uterine body using multiatlas labeling method from all the three orthogonal imaging orientations. JZ global mean is defined as the mean intensity of the global JZ contour.
3 JZ global mean *= Abbreviation of JZ global mean thickness. It is adopted from Gordts et al. 2015, which the measurement is based on JZ metrics automated derived from the mean of six JZ thickness measurements of the length of the entire uterine endometrium (endometrium circumference) (Figure 7b).
4 Myometrium/JZ ratio = Abbreviation of myometrial/JZ thickness ratio. It is equivalent to the terminology of the ¡°uterine wall ratio¡± used in ESHRE/ESGE Consensus [6] and the MUSA group guidelines [24]. The myometrium/JZ ratio is the myometrial thickness of the anterior or the posterior uterus divided by the JZmax of the same uterine wall, measured perpendicular to the endometrium on the same image plane.
5 JZ/total uterine thickness (JZ ratio) = Abbreviation of JZ/total uterine thickness. The total uterine wall thickness is summed from the thickness of the JZ and the outer myometrium. This terminology is also used in ESHRE/ESGE Consensus [6] as the term ¡°the JZ/uterine thickness ratio¡±. JZ ratio is defined as the percentage of the JZ thickness of the anterior or the posterior uterine wall divided by the total uterine wall thickness of the same uterine wall on the same image plane.
* = measured on both anterior and posterior wall (not per site); ** = JZ measurement is 2 mm intervals along four perpendicular lines from the basal endometrium to myometrial serosa; *** = reported as the sum of both anterior and posterior thickness; **** = a total of 144 thickness were calculated from the mid-sagittal or mid-coronal images; ***** = range. NA: not applicable; SA = short axis (sometimes the term is also used as the sagittal/sagittal oblique plane, or occasionally as a transverse plane); LA = long axis (sometimes the term is also used as the coronal/coronal oblique plane, or occasionally as a sagittal plane); ant = anterior; pos = posterior.
Table 3. Summary of JZ measurements in the general population (women undergoing hysterectomies or at risk for benign conditions, which does not meet the diagnostic criteria for adenomyosis). In this table, we intend to provide readers with a comprehensive review of past research data of healthy uterus. These data are from human cases in surgical procedure for any reason, but do not meet the diagnostic criteria for adenomyosis. Although most of the method (MRI protocol) is based on T2WI, if the method is based on T1WI, it is addressed in the table. JZ thickness in millimeters (mean ¡À standard deviation (SD)) measured from anterior uterine wall (ant) or posterior uterine wall (pos) in short axis (sagittal plane) or long axis (coronal plane). Age in years (mean ¡À SD) and hormonal effect are addressed in the table when data are available. ¡°?¡± = unavailable data or descriptive data; ¡°/¡± = data available but not presented by the authors; ¡°¨C¡± = measurement does not done from this parameter.
Table 3. Summary of JZ measurements in the general population (women undergoing hysterectomies or at risk for benign conditions, which does not meet the diagnostic criteria for adenomyosis). In this table, we intend to provide readers with a comprehensive review of past research data of healthy uterus. These data are from human cases in surgical procedure for any reason, but do not meet the diagnostic criteria for adenomyosis. Although most of the method (MRI protocol) is based on T2WI, if the method is based on T1WI, it is addressed in the table. JZ thickness in millimeters (mean ¡À standard deviation (SD)) measured from anterior uterine wall (ant) or posterior uterine wall (pos) in short axis (sagittal plane) or long axis (coronal plane). Age in years (mean ¡À SD) and hormonal effect are addressed in the table when data are available. ¡°?¡± = unavailable data or descriptive data; ¡°/¡± = data available but not presented by the authors; ¡°¨C¡± = measurement does not done from this parameter.
Authors (Year)/No. of Cases/Age (Reproductive Age and Cycle Day, Use of Hormonal Drugs)Measured Sites/Position (from SA or LA)JZ Metrics
JZmaxJZmeanJZ Global Max 1JZ Global Mean 2JZ Global Mean *,3Myometrium ThicknessAP JZ Thickness Ratio (JZ Differen-tial)Myome-trium/JZ Ratio 4JZ/Total Uterine Thickness (JZ Ratio) 5
Scoutt et al. (1991) [19]/n = 10/age 43.7 ¡À 6.2/?/NAant (mid-sagittal)5.0 mm *——–
pos (mid-sagittal)5.9 mm *——–
/ (mid-sagittal and all walls)——–
Dueholm et al. (2001) [42]/n = 59/age 25¨C48/day 5¨C12/NAThickest point and any axis2.5¨C7 mm **———
Hauth et al. (2007) [61]/n = 20/age 25¨C50/?/NAThickest point and (any axis)-7.0 ¡À 1.2 mm——-
Brown et al. (2012) [25]//n = 83/age 22¨C76/not specified/ NApos (mid-sagittal)9.5 ¡À 3.2 mm—-12.9 ¡À 4.0 mm—
Juang et al. (2015) [62]/n = 99/age 34¨C57/not specified/NAThickest point and (any axis)6.5 ¡À 1.5 mm——–
Champaneria et al. (2010) [12]/n = 20/age 18¨C49/not specified/ NAant or pos (any axis)8.5 ¡À 1.6 mm—-18.2 ¡À 3.8 mm *****–
* = range; ** = 50% percentile; *** = JZ measurement is 2 mm intervals along four perpendicular lines from the basal endometrium to myometrial serosa; **** = reported as the sum of both anterior and posterior thickness; ***** = mean total uterine wall thickness; ****** = range. NA: not applicable; SA = short axis (sometimes the term is also used as the sagittal/sagittal oblique plane, or occasionally as a transverse plane); LA = long axis (sometimes the term is also used as the coronal/coronal oblique plane, or occasionally as a sagittal plane); ant = anterior; pos = posterior.
Table 4. Summary of JZ measurements in healthy participants (no pathology or any uterine disease). Although most of the method (MRI protocol) is based on T2WI, if the method is based on T1WI, it is addressed in the table. JZ thickness in millimeters (mean ¡À standard deviation (SD)) measured from anterior uterine wall (ant) or posterior uterine wall (pos) in short axis (sagittal plane) or long axis (coronal plane). Age in years (mean ¡À SD) and hormonal effect are addressed in the table when data are available. ¡°?¡± = unavailable data or descriptive data; ¡°/¡± = data available but not presented by the authors; ¡°¨C¡± = measurement does not done from this parameter.
Table 4. Summary of JZ measurements in healthy participants (no pathology or any uterine disease). Although most of the method (MRI protocol) is based on T2WI, if the method is based on T1WI, it is addressed in the table. JZ thickness in millimeters (mean ¡À standard deviation (SD)) measured from anterior uterine wall (ant) or posterior uterine wall (pos) in short axis (sagittal plane) or long axis (coronal plane). Age in years (mean ¡À SD) and hormonal effect are addressed in the table when data are available. ¡°?¡± = unavailable data or descriptive data; ¡°/¡± = data available but not presented by the authors; ¡°¨C¡± = measurement does not done from this parameter.
Authors (Year)/No. of Cases/Age (Reproductive Age and Cycle Day, Use of Hormonal Drugs)Measured Sites/Position (from SA or LA)JZ Metrics
JZmaxJZmeanJZ Global Max 1JZ Global Mean 2JZ Global Mean *,3Myometrium ThicknessAP JZ Thickness Ratio (JZ Differen-tial)Myome-trium/JZ Ratio 4JZ/Total Uterine Thickness (JZ Ratio) 5
McCarthy et al. (1989) [63]/n = 14/?/day 5¨C8/NAThickest point and (any axis)¡Ü5 mm **——
Hirai et al. (1989) [64]/n = 7/age 25¨C41 /early proliferative phase/NAThickest point and (any axis)2¨C8 mm ***——
Scoutt et al. (1991) [19]/n = 10/age 43.7 ¡À 6.2/?/NAant (mid-sagittal)5.0 mm ******——
pos (mid-sagittal)5.9 mm ******——
Scoutt et al. (1993) [13]/n = 7/age 46 ¡À 5.0/day 1¨C10/NAThickest point and (any axis)¡Ü5 mm——–
Yamashita et al. (1993) [34]/n = 16/age 21¨C41/day 1¨C4/ 17% using hormonal drugsThickest point and (any axis)5.3 ¡À 1.9 mm——–
Togashi et al. (1994) [65]/n = 55/age 17¨C40/?/NAThickest point and (any axis)6 mm **——–
Tamai et al. (2005) [32]/n = 159/age 24¨C45/?/60% using hormonal drugsThickest point and (any axis)8.0 ¡À 2.0 mm——–
Hauth et al. (2007) [61]/n = 20/age 25¨C50/?/NAThickest point and (any axis)-7.0 ¡À 1.2 mm——-
Fang et al. (2013) [40]/n = 35/age 21¨C55/not specified/NAant or pos (any axis)6.3 ¡À 1.5 mm——–
Chen et al. (2014) [38]/n = 48/age 30.5/not specified/ NAThickest point and (any axis)7.47 ¡À 1.86 mm——–
Gordts et al. (2015) [18]/n = 72/age 22.8¨C50.5/day 8¨C12/NAPosterolateral quadrant; (SA/transverse)-5.7 ¡À 1.4 mm——-
Fang et al. (2015) [35]/n = 85/age 26¨C40/not specified/NAant or pos (any axis)7.8 ¡À 1.8 mm——–
Peng et al. (2020) [41]/n = 30/age 22¨C48/day 4¨C14/ NAThickest point and (any axis)5.2 ¡À 1.5 mm——–
Nakai et al. (2021) [37]/n = 28/ age 18¨C49/not specified/42% using hormonal drugsant or pos (any axis)5.0 ¡À 1.5 mm ****—-13.8 ¡À 2.5 mm ****—
* = measured on both anterior and posterior wall (not per site); ** = 50% percentile; *** = range; **** = excluding all the uterine pathologies and fibroids only including data which pass the inter-observer agreement test (83% of data). The data are based on a sample size of 23 cases. The measurements also excluded the cases with a history of pregnancy and use of hormonal drugs; ***** = a total of 144 thickness were calculated from the mid-sagittal or mid-coronal images; ****** = data in millimeters, mm. NA: not applicable; SA = short axis (sometimes the term is also used as the sagittal/sagittal oblique plane, or occasionally as a transverse plane); LA = long axis (sometimes the term is also used as the coronal/coronal oblique plane, or occasionally as a sagittal plane); ant = anterior; pos = posterior.
Table 5. Summary of JZ measurements in patients with adenomyosis. Most of the method (MRI protocol) is based on T2WI. If the method is based on T1WI, it is addressed in the table. JZ thickness in millimeters (mean ¡À standard deviation (SD)) measured from anterior uterine wall (ant) or posterior uterine wall (pos) in short axis (sagittal plane) or long axis (coronal plane). Age in years (mean ¡À SD) and hormonal effect are addressed in the table when data are available. ¡°?¡± = unavailable data or descriptive data; ¡°/¡± = data available but not presented by the authors; ¡°¨C¡± = measurement does not done from this parameter.
Table 5. Summary of JZ measurements in patients with adenomyosis. Most of the method (MRI protocol) is based on T2WI. If the method is based on T1WI, it is addressed in the table. JZ thickness in millimeters (mean ¡À standard deviation (SD)) measured from anterior uterine wall (ant) or posterior uterine wall (pos) in short axis (sagittal plane) or long axis (coronal plane). Age in years (mean ¡À SD) and hormonal effect are addressed in the table when data are available. ¡°?¡± = unavailable data or descriptive data; ¡°/¡± = data available but not presented by the authors; ¡°¨C¡± = measurement does not done from this parameter.
Authors (Year)/No. of Cases/Age (Reproductive Age and Cycle Day, Use of Hormonal Drugs)Measured Sites/Position (from SA or LA)JZ Metrics
JZmaxJZmeanJZ Global Max 1JZ Global Mean 2JZ Global Mean *,3Myometrium ThicknessAP JZ Thickness Ratio (JZ Differen-tial)Myome-trium/JZ Ratio 4JZ/Total Uterine Thickness (JZ Ratio) 5
Mark et al. (1987) [20]/n = 25/age 35¨C51/?/NAany axis, specific side excluded ** and thickest point10.7 ¡À 3.1 mm——–
Togashi et al. (1989) [66]/n = 40/age 30¨C46/?/NAThickest point and (any axis)?—-1.1 ¡À 1.0 ***
Hirai et al. (1989) [64]/n = 16/age 25¨C47 /early proliferative phase/NAThickest point and (any axis)14 mm ****——–
Scoutt et al. (1991) [19]/n = 8/age 43.7 ¡À 6.2/?/NAant (mid-sagittal)15.3 mm ****——–
pos (mid-sagittal)15.1 mm ****——–
Reinhold et al. (1996) [67]/n = 35/age 39/not specified/NAThickest point and (any axis)11.6 ¡À 5.4 mm——1.87 ¡À 0.54-
Novellas et al. (2001) [43]/n = 73/age 29¨C58/not specified/NAant or pos (LA)-9.8 ¡À 2.2 mm
13.3 ¡À 2.7 mm
–20.0 ¡À 2.0 mm2.04-
Tamai et al. (2005) [32]/n = 72/age 30¨C45/?/using hormonal drugsa specific site of any axis¡İ12 mm?——–
Bazot et al. (2009) [36]/n = 88/age 18¨C68/not specified/ NAant or pos (any axis)16.0 ¡À 4.0 mm—-15.0 ¡À 3.8 mm1.9 ¡À 0.3–
Bazot et al. (2012) [22]/n = 104/age 18¨C53/not specified/ NAant or pos (any axis)12.1 ¡À 3.7 mm—-16.6 ¡À 3.9 mm—
Kunz et al. (2014) [49]/n = 89/age 29¨C56/early proliferative phase/NAany axis¡İ8 mm **?——-
Chen et al. (2014) [38]/n = 96/age 37.5/not specified/ NAThickest point and (any axis)12.66 ¡À 3.91 mm——–
Fang et al. (2015) [35]/n = 89/age 18¨C40/not specified/NAant or pos (any axis)13.5 ¡À 3.6 mm——–
Brown et al. (2012) [25]/n = 142/age 22¨C76/not specified/ NApos (mid-sagittal)15.3 ¡À 5.5 mm—-15.8 ¡À 4.7 mm—
Nakai et al. (2021) [37]/n = 72/ age 18¨C49/not specified/ NAant or pos (any axis)14.0 ¡À 2.1 mm ****—-12.5 ¡À 2.0 mm ****—
* = measured on both anterior and posterior wall (not per site); ** = cases with either unilateral or well-defined lesions were assessed by exclude the specific side from the assessment of anteroposterior JZ thickness ratio; *** = data reported at luteal phase; **** = range; ***** = data in millimeters, mm, excluding all the uterine pathologies and fibroids. Only data which pass the inter-observer agreement test (75% of data) are included. The data are based on a sample size of 54 cases. Measurements also excluded cases with a history of pregnancy and use of hormonal drugs; ****** = a total of 144 thickness were calculated from the mid-sagittal or mid-coronal images. NA: not applicable; SA = short axis (sometimes the term is also used as the sagittal/sagittal oblique plane, or occasionally as a transverse plane); LA = long axis (sometimes the term is also used as the coronal/coronal oblique plane, or occasionally as a sagittal plane); ant = anterior; pos = posterior.
Table 6. Summary of JZ measurements in patients with infertility, endometriosis, or other condition. Most of the method (MRI protocol) is based on T2WI. If the method is based on T1WI, it is addressed in the table. JZ thickness in millimeters (mean ¡À standard deviation (SD)) measured from anterior uterine wall (ant) or posterior uterine wall (pos) in short axis (sagittal plane) or long axis (coronal plane). Age in years (mean ¡À SD) and hormonal effect are addressed in the table when data are available. ¡°?¡± = unavailable data or descriptive data; ¡°/¡± = data available but not presented by the authors; ¡°¨C¡± = measurement does not done from this parameter.
Table 6. Summary of JZ measurements in patients with infertility, endometriosis, or other condition. Most of the method (MRI protocol) is based on T2WI. If the method is based on T1WI, it is addressed in the table. JZ thickness in millimeters (mean ¡À standard deviation (SD)) measured from anterior uterine wall (ant) or posterior uterine wall (pos) in short axis (sagittal plane) or long axis (coronal plane). Age in years (mean ¡À SD) and hormonal effect are addressed in the table when data are available. ¡°?¡± = unavailable data or descriptive data; ¡°/¡± = data available but not presented by the authors; ¡°¨C¡± = measurement does not done from this parameter.
Authors (Year)/No. of Cases/Age (Reproductive Age and Cycle Day, Use of Hormonal Drugs)Measured Sites/Position (from SA or LA)JZ Metrics
JZmaxJZmeanJZ Global Max 1JZ Global Mean 2JZ Global Mean *,3Myometrium ThicknessAP JZ Thickness Ratio (JZ Differen-tial)Myome-trium/JZ Ratio 4JZ/Total Uterine Thickness (JZ Ratio) 5
Yamashita et al. (1993) [34] /n = 9 (uterine fibroids)/age 28¨C45/day 1¨C4/NAThickest point and (any axis)6.7 ¡À 1.6 mm——–
Yamashita et al. (1993) [34]/n = 9 (endometriosis)/age 26¨C47/day 1¨C4 /NAThickest point and (any axis)7.9 ¡À 1.6 mm——–
Hauth et al. (2007) [61]/n = 60 (fertile and infertile)/age 25¨C50/?/ NAThickest point and (any axis)-9.6 ¡À 2.0 mm
8.9 ¡À 2.2 mm
——-
Takahashi et al. (2013) [44] /n = 81 (endometriosis)/age 21¨C48/ not specified/ NAany axis with unaffected side and thickest point9.0 ¡À 2.1 mm——–
Peng et al. (2020) [41]/n = 65 (ovarian endometrioma with endometriosis uterine involvement)/age 22¨C48/day 4¨C14/NAThickest point and (any axis)10.9 ¡À 4.2 mm——–
Makled et al. (2014) [45]/n = 24 (unexplained infertility + leiomyoma)/age 26¨C40/day 7¨C10/NAThickest point and (any axis)8.5 ¡À 1.4 mm——–
Makled et al. (2014) [45]/n = 40 (unexplained infertility + history of abortion)/age 26¨C40/day 7¨C10/NAThickest point and (any axis)8.7 ¡À 1.5 mm——–
Makled et al. (2014) [45]/n = 101 (unexplained infertility without abortion history or leiomyoma)/age 26¨C40/day 7¨C10/NAThickest point and (any axis)7.6 ¡À 1.1 mm——–
Pinzauti et al. (2014) [46]/n = 23 (infertility + endometrioma)/age 25¨C37/day 2¨C5 day/NAThickest point and (any axis)7.47 ¡À 2.0 mm——–
Sofoudis et al. (2016) [47]/n = 39 (infertility + endometriosis or leiomyomas or previous myomectomy)/age 32.08 ¡À 4.13/ day 3¨C5/NAThickest point and (any axis)6.23 ¡À 1.25 mm——–
Sharma et al. (2019) [48] /n = 79 (endometriosis)/age 20¨C50/not specified/ NAThickest point and (any axis)9.0 ¡À 1.5 mm——–
Ramanathan et al. (2021) [39]/n = 30 (infertility)/age 21¨C34/not specified/ NAThickest point and (any axis)9.8 ¡À 2.0 mm——–
Kunz et al. (2014) [49]/n = 75 (infertility with endometriosis or polycystic ovarian syndrome)/age 29¨C56/early proliferative phase/ NA8¨C12 mm ***——–
* = measured on both anterior and posterior wall (not per site); ** = JZ measurement is 2 mm intervals along four perpendicular lines from the basal endometrium to myometrial serosa; *** = range. NA: not applicable; SA = short axis (sometimes the term is also used as the sagittal/sagittal oblique plane, or occasionally as a transverse plane); LA = long axis (sometimes the term is also used as the coronal/coronal oblique plane, or occasionally as a sagittal plane); ant = anterior; pos = posterior.
The previous research data may suggest that the difference in the plane used for image acquisition may produce a significantly different JZ thickness and, thus, may reduce the measurement precision between different planes or observers. Therefore, it is reasonable to adopt the same imaging orientations for MRI acquisition and the same measurement positions in order to obtain comparable data between different studies in the future. This will provide for more reproducible data to help establish JZ reference values and to reduce sampling bias due to imprecise measurement techniques.

9. Imaging Pitfall When Measuring JZ Metrics

There are a few potential sources of measurement inaccuracies associated with the MRI image acquisition or with the properties of the MRI image. These include (i) the image resolution and the contrast of the SI between the JZ and the myometrium, (ii) the locations (imaging plane), (iii) the inconsistent terminology for imaging orientation, (iv) the partial volume effect of the partial JZ thickness, and (v) the arbitrary identification of the borders of the JZ.
In general, a high resolution is needed for accurate JZ identification. In many past studies, image resolution was not provided [13,19,25,36,42,43,67,68]. In those studies which report the resolution of the pelvic MRI, the slice thickness/gap and the pixel/matrix size in mm are approximately 3¨C8 mm for the slice thickness and 0.39¨C0.89 mm for the in-plane resolution. The range of the spatial resolution of routine pelvic MRI can be considered as a potential risk for errors. For example, the recommendation from the Society of Radiologists in Ultrasound suggests a criterion for the maximum JZ thickness (JZmax) of 12 mm or greater for abnormality, which means the abnormal JZ may differ from the normal JZ thickness by approximately 4 to 10 mm, given that the normal JZmax is between 2¨C8 mm in the early proliferative phase [64]. Assuming a typical slice thickness of 5 mm, a typical pixel size of 0.8 mm, and a 12 mm threshold, the signal of the JZ could be contaminated by the myometrium. This is also true in the case of the interrupted appearance at the cornual region, where the extremely thin JZ signals could be overwhelmed by the higher signal of the outer myometrium, due to the partial volume effects of MRI. In our opinion, the effects of the partial volume can only be minimized by increasing the slice and the in-plane resolutions to at least the extent of the minimal changes in the JZ thickness at different cycle phases, or to the extent of differences in JZ thickness between the normal and diseased cases. A detailed discussion of the image resolution for the different types of MRI pulse sequences (e.g., T1W, T2W, T2*) is beyond the scope of this review.
As seen in Figure 3, the contrast of the JZ to the outer myometrium is typically high on a T2W image. However, if the relative contrast of the JZ and the myometrium on an MR image is too high, it may result in difficulty in defining the exact outer border of the JZ. This is because a low signal intensity of the JZ often has a slow transition to the higher intensity of the myometrium. The difference can be clearly visualized in a line intensity profile (Figure 6). This gradual change in the signal intensity makes it difficult to define an objective threshold for the outer border of the JZ. Unfortunately, different interpretations of the position of the outer boundary of the JZ have been used in different software with different threshold criteria. The threshold criteria applied to the outer border, and all of the other factors mentioned above, may cumulatively contribute to different results in JZ measurement, and may add up to a difference greater than the effects of normal cyclic variations (about 8% to 14%) or differences in diseased abnormalities (about 10¨C30%). As a result, measurements could be interpreted inconsistently, depending on which plane is used, and which position and border the user selects. A similar issue also exists for the definition of the endometrial¨Cmyometrium junction when automated programs and manual delineations (by human raters) are used [60].
A method that has higher accuracy and precision with minimal pitfalls can certainly improve the clinical feasibility of the measurements as objective indicators or criteria, and, thus, may help with the early detection of potential disease with less intra-/inter-observer variabilities than we currently have. Since all of these factors may coexist, a thorough investigation of the accuracy and precision of a given measuring method is important for interpretation.
With a well-designed evaluation strategy, such as the one suggested by Kottner et al. [69], future evaluation of the reliability of the measurement technique should include the following: an evaluation of (i) different observers with various training and/or educational backgrounds (e.g., radiologists, radiologic technologists, non-radiologic specialists with or without training), (ii) different observer experience levels (e.g., novice with 1 or 2 years of experience vs. expert with more than 10 years of experience), (iii) effects of normal variations in thickness and physiologic changes (e.g., across the menstrual cycle, across different reproductive ages), (iv) pathological variations in different disease stages and characteristics (e.g., mild, moderate, and severe adenomyosis based on pathology report and/or based on clinical symptoms), (v) the availability of the same subject from longitudinal (repeated scans) or cross-sectional measurements, and (vi) the effects of blinding or unblinding the measurements from the same images between repeated measurements over time (e.g., the case with the identical subject but different scan times in days or hours).

10. Future Perspectives

10.1. Disease Management

Adenomyosis can be focal or diffuse, which may result in limitations in its MRI diagnosis. The diagnosis with a focal adenomyosis is probably more complex than when the JZ is globally thick. It is well known that JZ thickness may vary as a function of the age and the menstrual cycle, but specific reference values for different ages and stages are not yet available. Some studies have found that a higher sensitivity and specificity were reached after the age variable was accounted for. In addition, the JZ may be thinner when ovarian function is pharmacologically controlled or suppressed by contraceptives. In other words, a different amount of circulating endogenous estrogen and progesterone during the menstrual cycle also affects the JZ thickness [34]. In our opinion, the current evidence does not provide enough information for making clinical decisions based on the JZ information, but it is useful as a confirmatory indicator. This is because the normal reference JZ values at different ages and with different hormonal levels or usage has not been clearly established. Similarly, thresholds for the diagnosis are also not systematically validated with various combinations of JZ metrics derived from different methods and measuring planes. Even though the assessment or pathology is the current practice of the diagnosis of adenomyosis, both methods have limitations and will need to be further evaluated [70]. Since the global JZ thickness measurement was found to have a high accuracy and low variability, future reference data from healthy controls at various conditions (e.g., age, cycle phase, etc.) are needed for establishing diagnostic or prognostic criteria, based on global JZ measurements.

10.2. Imaging Improvement for JZ Measurements

Future JZ MRI studies may also focus on enhancing measurement accuracy through signal intensity normalization to increase the confidence in defining the borders of the JZ by proposing and validating SI threshold criteria for the entire posterior uterine wall, by establishing consistent reproducible measuring positions across all studies, by providing more detailed recording of the key factors that could affect the accuracy of the measurements, by providing consistent and well-defined terms, and by potentially proposing computer-aided measurements for precision JZ measurements from a large study. The knowledge gained from these research areas may (1) provide reproducible and objective reference criteria for diagnosing adenomyosis from JZ measurements, (2) pave the way for early disease detection, (3) improve disease monitoring, and (4) help to develop personalized therapy.

Author Contributions

Conceptualization, P.-L.C. and Y.-C.L.; methodology, P.-L.C., E.A.H. and Y.-C.L.; validation, P.-L.C. and Y.-C.L.; formal analysis, P.-L.C.; investigation, P.-L.C. and Y.-C.L.; resources, P.-L.C., E.A.H. and Y.-C.L.; data curation, P.-L.C.; writing¡ªoriginal draft preparation, P.-L.C.; writing¡ªreview and editing, P.-L.C., E.A.H. and Y.-C.L.; supervision, Y.-C.L.; funding acquisition, Y.-C.L. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported in part by Kaohsiung Medical University Research Center (Grant no. KMU-TC109A01-03 and KMU-TC108B04) and by the National Science Council of Taiwan (NSC MOST 109-2314-B-037-108-MY3, MOST109-2314-B-037-120-MY3).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors would like to thank the National Science Council of Taiwan and Kaohsiung Medical University for financial supports. The authors would also like to thank the Boston University School of Medicine postdoctoral research fellowship (supported by the National Institute of Health, NIH R25CA089017 and U56CA101098) for training P.-L.C. in research skills on diagnostic imaging.

Conflicts of Interest

All authors have no conflicts of interest to declare. There was no special relationship or interest with the funding sources.

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Figure 1. MRI imaging planes are in the body¡¯s orthogonal orientations (coronal (left), transverse (middle), and sagittal (right). The different anatomical positions of the uterus (e.g., anteversion in red, midposition in blue, or retroversion in green) within these orthogonal planes affects whether a specific imaging plane will correspond to the proper anatomical orientation of the uterine body. For example, because of the anteversion of the uterus (red dashed line with arrow head), the uterine body is visualized obliquely with respect to the coronal body plane. Similar to the retroversion of the uterus (green dashed line with the arrow head), the uterine body is also obliquely visualized. Only the case with an upright orientation (blue dashed line with the arrow head in the middle) will align with the coronal body plane of an imaging plane.
Figure 1. MRI imaging planes are in the body¡¯s orthogonal orientations (coronal (left), transverse (middle), and sagittal (right). The different anatomical positions of the uterus (e.g., anteversion in red, midposition in blue, or retroversion in green) within these orthogonal planes affects whether a specific imaging plane will correspond to the proper anatomical orientation of the uterine body. For example, because of the anteversion of the uterus (red dashed line with arrow head), the uterine body is visualized obliquely with respect to the coronal body plane. Similar to the retroversion of the uterus (green dashed line with the arrow head), the uterine body is also obliquely visualized. Only the case with an upright orientation (blue dashed line with the arrow head in the middle) will align with the coronal body plane of an imaging plane.
Applsci 11 11096 g001
Figure 2. Diagram of the structure of the myometrium based on the freeze dissection of the uterus (the four-layer concept) and the JZ model. (a) Four-layer concept in the myometrium with a cut at the coronal view (gray, black, red, blue), combined with the anatomic correlation of the JZ concept (JZ, yellow). (b) The structure is illustrated in the sagittal plane. (c) The structure is illustrated in the transverse plane (reproduced with permission from Wetzstein (Die musculatur des uterus ausserhalb der Schwangerschaft (1990)) [1] and Goerttler (Die Anordnung, Histologie und Histogenese der glatten Muskulatur im Corpus uteri von Erwachsenen (1930)) [2]).
Figure 2. Diagram of the structure of the myometrium based on the freeze dissection of the uterus (the four-layer concept) and the JZ model. (a) Four-layer concept in the myometrium with a cut at the coronal view (gray, black, red, blue), combined with the anatomic correlation of the JZ concept (JZ, yellow). (b) The structure is illustrated in the sagittal plane. (c) The structure is illustrated in the transverse plane (reproduced with permission from Wetzstein (Die musculatur des uterus ausserhalb der Schwangerschaft (1990)) [1] and Goerttler (Die Anordnung, Histologie und Histogenese der glatten Muskulatur im Corpus uteri von Erwachsenen (1930)) [2]).
Applsci 11 11096 g002
Figure 3. Zonal anatomy of the normal uterus from a premenopausal woman (long axis). This visualization of the uterus is more analogous to a coronal/coronal oblique/long-axis orientation. The zonal anatomy of the uterus is clearly defined in (a¨Cc), with a thin, linear hyperintense signal of the endometrial cavity (yellow arrows); an intermediate signal endometrial layer (white arrows) just adjacent to the center endometrial cavity line; the low signal intensity of the inner JZ (orange arrows); and a more uniformly intermediate myometrium surrounding the JZ. The urinary bladder (blue arrows) is located anterior to the uterus, and the vagina (green arrows) is located inferior to the uterus (inferior). The vagina is separated by the endometrial cavity at the internal os of the cervix. (a¨Cc) are three cases of different uterine positions (anteversion, midposition, and retroversion).
Figure 3. Zonal anatomy of the normal uterus from a premenopausal woman (long axis). This visualization of the uterus is more analogous to a coronal/coronal oblique/long-axis orientation. The zonal anatomy of the uterus is clearly defined in (a¨Cc), with a thin, linear hyperintense signal of the endometrial cavity (yellow arrows); an intermediate signal endometrial layer (white arrows) just adjacent to the center endometrial cavity line; the low signal intensity of the inner JZ (orange arrows); and a more uniformly intermediate myometrium surrounding the JZ. The urinary bladder (blue arrows) is located anterior to the uterus, and the vagina (green arrows) is located inferior to the uterus (inferior). The vagina is separated by the endometrial cavity at the internal os of the cervix. (a¨Cc) are three cases of different uterine positions (anteversion, midposition, and retroversion).
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Figure 4. Example of a healthy uterus illustrated in three different anatomical orientations of the endometrium canal. Image (a) represents MRI acquisition with an imaging plane positioned parallel to the endometrium canal and perpendicular to the fundus of the uterus (coronal oblique view, red line). Image (b) and image (c) represent MR image slices that are perpendicular to the endometrium canal, as indicated by yellow and blue lines in (a), respectively. In order to define the anatomical long-axis and short-axis orientation, image (a) can be viewed as the anatomical long axis (long axis), which was acquired with an imaging plane that is perpendicular to the short axis (the sagittal oblique orientation). The sagittal oblique orientation may be positioned either at the uterine body (b) or at the fundus of the uterus (c). (a): endometrium = yellow arrow, JZ = orange arrow, myometrium = magenta arrow, serosa = green arrow, parametrial fat = white arrow.
Figure 4. Example of a healthy uterus illustrated in three different anatomical orientations of the endometrium canal. Image (a) represents MRI acquisition with an imaging plane positioned parallel to the endometrium canal and perpendicular to the fundus of the uterus (coronal oblique view, red line). Image (b) and image (c) represent MR image slices that are perpendicular to the endometrium canal, as indicated by yellow and blue lines in (a), respectively. In order to define the anatomical long-axis and short-axis orientation, image (a) can be viewed as the anatomical long axis (long axis), which was acquired with an imaging plane that is perpendicular to the short axis (the sagittal oblique orientation). The sagittal oblique orientation may be positioned either at the uterine body (b) or at the fundus of the uterus (c). (a): endometrium = yellow arrow, JZ = orange arrow, myometrium = magenta arrow, serosa = green arrow, parametrial fat = white arrow.
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Figure 5. Long-axis view of the uterus with interrupted JZ in the fundus (a,b) and continuous JZ (c,d). For cases with interrupted JZ in the fundus (a,b, blue arrows), the thickness of the JZ is better measured at the locations without interruption (red arrows) for JZ evaluation. Only the uninterrupted JZ location (red arrows) should be used for valid JZ measurements, as recommended by the Morphological Uterus Sonographic Assessment (MUSA) group. However, an uninterrupted JZ at the cornual region on a continuous JZ case (c,d, green arrows) can also be used.
Figure 5. Long-axis view of the uterus with interrupted JZ in the fundus (a,b) and continuous JZ (c,d). For cases with interrupted JZ in the fundus (a,b, blue arrows), the thickness of the JZ is better measured at the locations without interruption (red arrows) for JZ evaluation. Only the uninterrupted JZ location (red arrows) should be used for valid JZ measurements, as recommended by the Morphological Uterus Sonographic Assessment (MUSA) group. However, an uninterrupted JZ at the cornual region on a continuous JZ case (c,d, green arrows) can also be used.
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Figure 6. (a) The short-axis view of the uterus with the signal intensity (SI) profiles perpendicular to the endometrium at the body of the uterus. The SI profile presents an evaluation of locations of the borders of JZ layer. The black arrows indicate the inner border, and the gray arrows indicate the outer border of the JZ. The color arrows from the demarcated outer border of the JZ indicate different locations based on different criteria: Orange is an estimation from the outer border of low signal intensity band (SI < 250 as suggested in ESHRE/ESGE 2013 Consensus [6]); Green is an estimation from the outermost boundary of the JZ that excludes myometrium which has an increasing signal intensity at the end of the SI profile (estimated at the peak SI as suggested by JZtool [16,17]); Blue is an estimation from the visually defined transition zone between the JZ and myometrium (e.g., MUSA group guideline [24]). (b) Different criteria for the demarcation of the outer border of the JZ. JZ metrics using the thickness from the maximum JZ thickness (JZmax), the mean JZ thickness (JZmean), or the mean of the global JZ thickness (JZglobal). Due to a gradual transition of signal intensity from the JZ to the outer myometrium, the outer border of the JZ cannot always be easily identified (green arrows). Note, JZmax, JZmean, and JZglobal vary with the selected outer border.
Figure 6. (a) The short-axis view of the uterus with the signal intensity (SI) profiles perpendicular to the endometrium at the body of the uterus. The SI profile presents an evaluation of locations of the borders of JZ layer. The black arrows indicate the inner border, and the gray arrows indicate the outer border of the JZ. The color arrows from the demarcated outer border of the JZ indicate different locations based on different criteria: Orange is an estimation from the outer border of low signal intensity band (SI 40%: ESHRE/ESGE Consensus [6]
>50%: Kunz [50,51]
Myometrium/JZ ratio<2.2 [43]
<1.5 [50]
LAP = measured from the long axis (coronal) plane (analog to long axis/coronal/coronal oblique) of the uterus; SAP = measured from the short axis (sagittal) plane (analog to short axis/sagittal/sagittal oblique) of the uterus; JZmax: the maximal thickness of JZ (perpendicular to the endometrium).
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Chen, P.-L.; Hoffman, E.A.; Lin, Y.-C. MRI Evaluation of the Uterine Junctional Zone. Appl. Sci. 2021, 11, 11096. https://doi.org/10.3390/app112311096

AMA Style

Chen P-L, Hoffman EA, Lin Y-C. MRI Evaluation of the Uterine Junctional Zone. Applied Sciences. 2021; 11(23):11096. https://doi.org/10.3390/app112311096

Chicago/Turabian Style

Chen, Pei-Lun, Eric A. Hoffman, and Yi-Chun Lin. 2021. "MRI Evaluation of the Uterine Junctional Zone" Applied Sciences 11, no. 23: 11096. https://doi.org/10.3390/app112311096

APA Style

Chen, P. -L., Hoffman, E. A., & Lin, Y. -C. (2021). MRI Evaluation of the Uterine Junctional Zone. Applied Sciences, 11(23), 11096. https://doi.org/10.3390/app112311096

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