Fetal abdominal magnetic resonance imaging

European Journal of Radiology 57 (2006) 278–293

Fetal abdominal magnetic resonance imaging Peter C. Brugger a,∗ , Daniela Prayer b a

Center of Anatomy and Cell Biology, Integrative Morphology Group, Medical University of Vienna, Waehringerstrasse 13, 1090 Vienna, Austria b Department of Radiology, Medical University of Vienna, Waehringerg¨ urtel 18-20, 1090 Vienna, Austria

Received 11 November 2005; received in revised form 14 November 2005; accepted 16 November 2005

Abstract This review deals with the in vivo magnetic resonance imaging (MRI) appearance of the human fetal abdomen. Imaging findings are correlated with current knowledge of human fetal anatomy and physiology, which are crucial to understand and interpret fetal abdominal MRI scans. As fetal MRI covers a period of more than 20 weeks, which is characterized not only by organ growth, but also by changes and maturation of organ function, a different MR appearance of the fetal abdomen results. This not only applies to the fetal intestines, but also to the fetal liver, spleen, and adrenal glands. Choosing the appropriate sequences, various aspects of age-related and organ-specific function can be visualized with fetal MRI, as these are mirrored by changes in signal intensities. Knowledge of normal development is essential to delineate normal from pathological findings in the respective developmental stages. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Fetus; Gastrointestinal tract; Adrenal; Liver; Spleen; MRI

1. Introduction

2. Materials and methods

The earliest fetal MRI studies were performed to obtain a better assessment of the fetal brain [1,2]. In the late 1990s, occasional reports mentioned the possibilities of fetal MRI in visualizing extra-CNS organ systems [3–6], with an emphasis on fetal lungs and thoracic malformations [7–12]. It was not until recently that interest shifted to imaging of the abdomen and gastrointestinal tract [13–21]. However, many of these reports were pictorial essays or were based on small series. Because a more systematic approach is lacking, the present work attempts to address this gap and tries to correlate imaging findings with current knowledge of human fetal anatomy and physiology, which are important in understanding and interpreting fetal abdominal MRI.

MR imaging was performed on a 1.5 T magnet (Philips Gyroscan, Philips, Best, The Netherlands) using a fiveelement phased-array surface coil. Imaging protocols to study the fetal abdomen include T2-weighted TSE sequences in three orthogonal planes of the fetal body, usually using an echo time of 100 ms, but, in certain situations, longer echo times (280 ms) may be indicated. Basically, frontal planes are the most suitable (FOV adjusted to fetal size and maternal body habitus, ranging from 200 to 350 mm), because they cover the entire fetus with the fewest number of slices (Fig. 1). For axial scans, the minimum FOV is about 170 mm. In addition to steady-state free-precession sequences (FOV 260–350 mm), frontal and/or sagittal T1weighted, fast low-angle shot sequences (TR/TE, shortest, 4.6 ms; FOV 265–350 mm; slice thickness 5 mm; gap 0.5 mm; performed in breath-hold; 15 slices in 15 s) are routinely used. Single-shot GRE echo-planar sequences are acquired in the sagittal or frontal planes and dynamic steadystate free-precession sequences may be used to demonstrate

∗

Corresponding author. Tel.: +43 1 4277 61163; fax: +43 1 4277 61141. E-mail address: [email protected] (P.C. Brugger).

0720-048X/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2005.11.030

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Fig. 1. Comparison of various sequences used in fetal abdominal imaging. Corresponding frontal slices of a fetus at 31 GW. (a) T2-weighted sequence (TE 100 ms). (b) Steady-state free-precession sequence. (c) T2-weighted sequence with long echo time. (d) T1-weighted sequence.

bowel motility. Although fetal breathing movements become more abundant and pronounced in older fetuses, this does not interfere with image quality.

3. Normal fetal abdominal anatomy In the complex embryology of the gastrointestinal tract and abdomen, all the major steps are completed by 18 gestational weeks (GW). However, it seems appropriate to briefly summarize fetal abdominal anatomy at the time when fetal MRI begins, and focus on the particularities of fetal abdominal organs within the time period covered by fetal MRI. Organ anatomy relevant to the time period covered by fetal MRI will precede each section. In general, differences from the adult pattern are mainly due to different proportions and topographical relationships. The fetal abdomen is dominated by the large and symmetric liver (Fig. 2), which nearly reaches the iliac crests. Since the fetal pelvis is very small, the filled urinary bladder may occupy considerable portions of the abdomen in older fetuses (>30 GW). The retroperitoneum is occupied by the kidneys and large adrenal glands. The time period covered by fetal MRI is characterized by further growth in overall dimensions and differentiation on a histological level.

fetal development, a different appearance results at different gestational ages, characteristic of each developmental stage. Although fetal swallowing is reported to start at 9–10 GW [22,23], significant amounts of amniotic fluid do not enter the fetal bowels (except for the stomach) before 25 GW, to serve as a natural contrast medium. The amniotic fluid volume swallowed increases steadily, with a term fetus swallowing as much as 750 ml/day [23]. Indeed, intestinal fluid filling will be less conspicuous in cases of anhydramnios or severe oligohydramnios (as a consequence of premature rupture of membranes or renal agenesis). 4.1. Stomach 4.1.1. Anatomy The fetal stomach resembles the adult stomach in shape and continuously increases in size with advancing gestation. The differentiation into three muscle layers is already present around 11–12 GW, with the pyloric region being more muscular in the fetus [24]. Sporadic peristalsis of the fetal stomach can be demonstrated from 14 GW onward [25]. Gastric motility parallels the maturation of gastric innervation, with pyloric innervation achieving an adult like profile by 23–23 GW [26] and the muscles of the pyloric region reaching a complete adult form by 27 GW [27]. By that time, grouped peristalsis is observed in all fetuses, which is considered to be responsible for gastric emptying [25,28].

4. Imaging of the fetal gastrointestinal tract While in adults information about the gastrointestinal tract (GIT) is gained by using various contrast media, one has to rely on “natural” contrast media in the fetal setting: basically the amniotic fluid and intestinal contents such as meconium. In addition to the dimensions of the fetal gastrointestinal tract, the presence and abundance of these natural contrast media determine the ability of fetal MRI to depict intestinal anatomy. Since the existence of these natural contrast media and their distribution within the fetal GIT correlates with

4.1.2. Imaging The stomach should always be recognizable as a fluidfilled structure in the left upper abdomen from 18 GW onward (Fig. 1, Figs. 3 and 4), presenting with variable amounts of filling. The stomach wall itself is already visible by 20 GW, and, in later stages of gestation (>29 GW), mucosal folding may also be demonstrated. The region of the pylorus and proximal parts of the duodenum can occasionally also be visualized. Since fluid within the fetal stomach consists of swallowed amniotic fluid, the hyperintense T2-weighted sig-

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Fig. 2. Fetal torso around 20 GW. (a) Abdominal situs demonstrating the large liver, with the falciform ligament inserting left of the midline. (b) Small intestines and liver removed.

nal corresponds to T1-weighted hypointensity. An exception to that rule includes situations with intra-amniotic bleeding, when swallowed diluted blood leads to T1-weighted hyperintensity of the gastric contents. 4.1.3. Anomalies Position: Abnormal intraabdominal position of the stomach indicates situs anomalies. An intrathoracic stomach is

usually seen in left-sided congenital diaphragmatic hernias (CDH), or, less frequently, in gastric herniation [4,29]. Size: Poor visualization of the stomach because of small amounts of gastric fluid should raise the suspicion for esophageal atresia, especially when this condition is associated with polyhydramnios. With MRI, demonstration of the stomach is possible in these cases [18]. A small stomach (microgastria) may been seen in right-sided isomerism,

Fig. 3. Fetus at 22 GW. (a, b) Frontal T2-weighted images. Characteristic spotty appearance of the fetal abdomen typical for this stage. Fluid-filled stomach, stomach wall, and pyloric region are recognizable.

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Fig. 4. Fetus at 31 GW. (a) Frontal T2- and (b) corresponding T1-weighted image. T2-weighted hyperintense signals of the jejunum correspond to T1-weighted hyperintensity, comparable to hepatic tissue.

Fig. 5. Fetus at 26 GW. (a, b) Frontal T2-weighted images showing classical “double bubble” sign. The incisure in (a) is due to a pyloric sphincter.

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whereas an enlarged stomach is characteristic of gastric outlet obstruction or duodenal atresia/stenosis (Fig. 5). Gastric duplication cysts have been reported using fetal MRI [30]. 4.2. Small intestines 4.2.1. Anatomy At 20–21 GW, the length of the small intestines measures 93–98 cm [31,32] and both the jejunum and ileum have mean diameters of 3 mm, increasing in subsequent weeks, with the jejunum showing larger dimensions [33]. Maturation occurs in a cranio-caudal direction, and, by mid-gestation (20–25 GW), the intestinal architectural and functional features are highly similar to those of the newborn [34,35]. 4.2.2. Imaging Up to 24–25 GW, the small intestines are only minimally fluid-filled (2–3 mm in diameter) and thus present with T2-weighted signals that are iso- or hypointense to muscle, resulting in a spotty appearance of the fetal abdomen typical for this developmental stage (Fig. 3). Some fluid-filled loops are occasionally detectable. As proximal and distal small intestines show similar signals, differntiation between both is not possible by that time. Likewise, distinction between small and large bowel is only possible by topography. Appreciable amounts of fluid appear only after 25 GW. This observation is attributable to increasing amounts of swallowed amniotic fluid and the fact that gastric emptying develops rapidly after 24 GW [28]. Following 26–27 GW, fluid-filled small bowel loops become apparent, predominantly in the left abdominal moiety, presenting with T2weighted hyperintense signals (Fig. 4a), and a distinguishable wall. In contrast to the stomach, fluid within the proximal small intestines may not show T1-weighted hypointensity, but presents with a signal intensity similar to muscle or even liver (Fig. 4b). This may reflect the secretory activity of the proximal small intestine, liver, and pancreas, since the substances leading to the hyperintense T1-weighted signal of meconium are produced in the upper digestive tract. Beyond 30 GW, longer, fluid-filled jejunal segments will be constantly found, with diameters up to 7–8 mm, and the bowel wall itself can be well-demonstrated on heavily T2-weighted sequences (Fig. 1). By 35 GW, the non-fluid-filled jejunum loops can also be identified, since the bowel wall can be demarcated from its contents. When fluid-filled, the normal duodenum sometimes can be visualized. Due to fluid resorption in the distal small intestines, the intestinal content shows intermediate to low T2-weighted signal intensities and, consequently, displays T1-weighted hyperintensity, since the intestinal content closely resembles meconium. From 25 GW onward, these T1-weighted hyperintense ileal loops seen in the lower right quadrant of the abdomen may be differentiated from the ascending colon by their topography and smaller cross-sectional diameters (3–4 mm).

4.2.3. Anomalies Intrathoracic small bowel is usually seen in left-sided CDH, and, less frequently, in right-sided CDH. Extracorporal small intestines are found in gastroschisis and omphalocele [18]. In the presence of intra-amniotic bleeding, fetal swallowing of bloody fluid results in more T1-weighted hyperintensity of the fetal intestines, corresponding to the hyperechogenic bowel at US examination [36]. The small intestines are frequently the site of stenosis, obstruction, or atresia. Fetal MRI can help to localize the anatomical site of obstruction [13,17]. Stenosis of the proximal intestines is easily recognized by the presence of the “doubble bubble” sign, with marked dilatation of the duodenum [17] (Fig. 5). Furthermore, fetuses with atresia or high-grade stenosis of the duodenum or proximal jejunum are more likely to develop polyhydramnios [37], supplying further evidence for the role of swallowing and intestinal resorption in amniotic fluid volume regulation [38]. Small bowel atresia/stenosis is more common than duodenal atresia and presents with widely dilated bowel loops proximal to the site of stenosis. The content of the dilated intestinal loops may present with T1-weighted hyperintensity corresponding to intermediate signals on T2-weighted and steady-state free-precession sequences (Fig. 6). Moreover, peristalsis can be demonstrated using dynamic sequences (Fig. 7). With fetal MRI, it is also possible to assess the postatretic bowel segments and to demonstrate multiple atresias [17]. 4.3. Large intestines 4.3.1. Anatomy By 18–19 GW, the left colonic flexure and the descending colon have achieved their retroperitoneal position [39,40], while the transverse and ascending colon, together with the caecum, form a diagonal limb coursing from the left colonic flexure to the right iliac crest [39,41,42] (Fig. 1b). The future right colonic flexure is only moderately indicated as a kink ventral to the descending part of the duodenum [39,43] (Fig. 2b, Fig. 8). The ileocaecal region becomes fixed in the fifth fetal month [39]. The fetal caecum is positioned at the level of the right iliac crest [41]; its final position within the right iliac fossa is reached later in development. As in adults, the length and position of the sigmoid and transverse colon are quite variable [44]. Development of colonic haustra starts at the ascending colon [44] and, histologically, the haustra can be demonstrated as early as 10–11 GW [45]. The maximum colon diameters increase with advancing age [14] (from 3–4 mm by 20 GW to 8–15 mm at term [44]) and may be found in either part of the colon. Although the functional components of the anal sphincter do not differentiate before 30 GW, anal continence is present at 22 GW [46], which may be due to increased meconial viscosity.

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Fig. 6. Fetus (28 GW) with gastroschisis and jejunal atresia. (a) Frontal T2-weighted image shows intermediate signal intensity of distended jejunal loops (when compared to fluid within the stomach and urinary bladder). (b) Frontal steady-state free-precession image also shows intermediate signal intensity. (c) Frontal T1-weighted image reveals hyperintense signal similar to meconium.

The early mesenteric fixation of the descending colon makes its position a useful criterion by which to differentiate between the retroperitoneal or intra-abdominal location of “abdominal” masses. 4.3.2. Imaging Fetal MRI of the large intestines depends, in large part, on the signal characteristics of meconium. Meconium is the material that collects in the distal small intestines, and subsequently, the colon in normal fetuses, and consists of intestinal secretions and desquamated intestinal epithelium, as well as swallowed amniotic fluid and epidermal cells [47]. Meco-

nium is approximately 72% water, and nearly 80% of its dry weight is comprised of mucosubstances [22]. Meconium usually appears hypointense on T2-weighted sequences and has intermediate signal intensity on steady-state freeprecession sequences (Fig. 1). The T1-weighted hyperintense signal properties of meconium allow selective demonstration of the meconium-filled parts of the colon. However, the substance responsible for this T1-weighted hyperintensity of meconium is still unknown. Variations in both T1and T2-weighted signal intensities can be observed and are probably due to differences in meconium composition and concentration.

Fig. 7. Fetus (35 GW) with small bowel stenosis: 10 frames of a dynamic study (every second image) demonstrating marked peristalsis in the distended jejunal segment.

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Fig. 9. Fetus at 35 GW. Axial T2-weighted image through the lower abdomen. Situs inversus, the vermiform appendix can be recognized the left lower abdomen (arrowhead).

Fig. 8. Meconium-based colonography in a fetus at 26 GW. All parts of the colon are meconium-filled. Note the oblique course of the transverse and ascending colon.

As meconium accumulates in the fetal colon from the 19th GW onward, the rectum becomes filled first, showing characteristic topographical relationships to the fetal urinary bladder [14,17]. Though basically a successive “filling” from distal to proximal, variable progression into the descending colon may depend on sigma length. Occasionally, gaps may be found and some parts of the colon may be devoid of meconium. By 22/23 GW, the left colonic flexure is easily recognized by its cranial and dorsal position. Next, the transverse and ascending colon become recongizable, usually demonstrating a transverse or oblique course (Fig. 8). Because of their close relation to the fetal liver, which has intensities similar to that of the colon, the transverse and ascending colon are difficult to recognize on T2-weighted images. Around 25 GW, the whole colon is usually meconiumfilled and maximum intensity projections allow colonography that provides images similar to those obtained after barium enema [48] (Fig. 8). The topography, flexures, and parts of the fetal colon, including the variable sigmoid, can be identified, as well as haustra that become apparent with advancing age.

The colon wall itself cannot be distinguished on T2- or T1weighted images. On steady-state free-precession sequences, identification of the large bowel wall is possible, since the intermediate signal intensity of meconium contrasts well with the hypointense-appearing wall, allowing demonstration of the colonic haustra as well. Given its small dimensions [49], the vermiform appendix can only rarely be demonstrated with prenatal MRI (Fig. 9). 4.3.3. Anomalies Position: In left-sided CDH, the sigmoid, descending colon, and the left colonic flexure are in situ, while variable parts of the transverse and the whole ascending colon are usually found intrathoracically. The diameters of the intrathoracic colon segments usually exceed those of the intraabdominal areas. In gastroschisis, the colon is usually extra-corporeal, except for the sigmoid and rectum. Colon malrotation or non-rotation is usually part of heterotaxy syndromes [50,51] or may occur together with large intrabdominal masses [52]. Anal atresia may be diagnosed early, since the rectum should be filled first. Additional anomalies should be searched out, since associated vertebral anomalies and a short spinal cord will help to establish the diagnosis of a caudal regression syndrome (VATER association). However, meconium filling of the rectum and anal canal may be affected by the filling of the urinary bladder. Massive filling of the urinary bladder may “squeeze” out the meconium of the rectum. In cloacal malformations, the rectum may present with an abnormally low T1-weighted signal [14], indicating a

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fistula in the urinary bladder. In congenital megacolon (Hirschsprung’s disease), the dilatated rectum has reportedly shown intermediate T2-weighted signal intensity [53].

5. Liver 5.1. Anatomy The fetal liver is rather symmetric since the left hepatic lobe is larger than in the adult (Fig. 2). Data on organ growth are available from necropsy studies [54], as well as in vivo fetal MRI [55,56]. From the fifth to the ninth fetal month, the physiological left liver is a little over one-tenth larger than the right [57]. Differences between the physiological liver lobes result, in part, from the blood supply of the fetal liver, which is different than in the adult: the portal branches of the umbilical vein supply the left hepatic lobe with highly oxygenated blood, while the right hepatic lobe receives blood with a lower oxygen saturation from the portal vein [57,58]. During the fetal period, the liver is a hematopoietic organ from 6 to 8 GW onward, with the right lobe showing greater hematopoietic activity than the left [57]. In the last trimester, hepatic hematopoiesis decreases progressively. Moreover, the fetal liver is an important site of (non-heme) iron storage, which may be as high or even higher than in adults. Corresponding to organ growth, the total iron content has been reported to increase with advancing gestational age [59], but fetuses of comparable gestational age and body weight vary considerably with respect to liver iron storage content [60], as well as total liver iron content [61]. However, in a more recent study, Faa et al. [62] could not detect a significant correlation between liver iron concentration and gestational age, but observed a tendency of the left hepatic lobe to accumulate more iron. 5.2. Imaging Fetal hepatic tissue shows T2-weighted hypointensity similar to muscle, corresponding to diffusely increased signal intensity on T1-weighted sequences (Figs. 2 and 4), which is fairly constant during pregnancy (when compared to amniotic fluid) and similar to maternal liver. While T1- and T2-weighted sequences do not show differences between the physiological right and left liver lobes, these may be documented using echoplanar imaging (EPI) (Fig. 10). Using EPI, Duncan et al. [63] demonstrated changes in signal intensities of the fetal liver between 20 and 26 GW, which were thought to reflect changes in fetal liver erythropoiesis. In general, three stages of the EPI appearance of the fetal liver may be distinguished: marked hypointensity up to 20/22 GW; a decrease in signal intensity up to 26/27 GW and then, another increased hypointensity subsequently (Fig. 11). Nevertheless, there are exceptions to that rule and our preliminary experience suggests that these variances may be fetus-specific. More recently, Semple et al. [64], using

Fig. 10. Fetus at 27 GW. Frontal echoplanar image reveals different signal intensities of right and left hepatic lobes (dividing line between physiologic hepatic lobes runs vertically through the biliary bladder). This may reflect better oxygenation of the left hepatic lobe or increased iron storage (fetus showed same findings 4 weeks later).

T2* imaging, demonstrated signal changes in the fetal liver, depending on oxygen saturation. Intrahepatic vessels are best demonstrated with steadystate free-precession sequences, which also allow visualization of the ductus venosus as early as 21 GW. On T2weighted sequences, intrahepatic vessels are less conspicuous, except in cases of stasis associated with heart failure (Fig. 12). 5.3. Anomalies Position: Intrathoracic hepatic lobes may be seen in CDH and can be demonstrated using T1-weighted sequences. Alternatively, echoplanar sequences may be used (Fig. 11c) to image the liver in young fetuses in which T1-weighted imaging may be complicated. A partly extracorporeal liver is frequently found in omphaloceles [15,16,19]. Though rare, liver tumors, such as hepatoblastomas, infantile hemangioendotheliomas [4], or hepatic hemangiomas [20], can be demonstrated with fetal MRI. Iron overload, as in fetal hemochromatosis, may be detected with fetal MRI by the marked signal intensity reduc-

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Fig. 11. Frontal echoplanar images of fetuses at different GW show signal intensity changes in the fetal liver. (a) At 22 GW, the liver shows marked hypointensity. (b) Fetus (24 GW) liver shows bright signal. (c) fetus (27 GW) with left-sided congenital diaphragmatic hernia. The intrathoracic left hepatic lobe is easily recognized by its hypointense signal. (d) At 30 GW, the fetal liver again shows hypointense signals, though less pronounced than at 22 GW.

tion of the fetal liver on T2* sequences [65,66]. Morevoer, when associated with cirrhosis, the fetal liver also shows reduced T1-weighted signal intensity (Fig. 13). 6. Gall-bladder (biliary bladder) 6.1. Anatomy Before 16–17 GW, the gallbladder is nearly entirely embedded within the inferior surface of the liver. After the 18th GW, the gallbladder bed becomes progressively more shallow, and protrusion of the gallbladder below the inferior hepatic surface gets more pronounced with advancing gestation [67]. In contrast to the adult, the tip of the fetal gallbladder fundus usually does not protrude beyond the inferior margin of the liver [67]. The size of the fetal gallbladder increases with age [68,69] and is subject to a daily sinusoidal contractility cycle [69], which, to some extent, may explain variations in size.

6.2. Imaging The fetal gallbladder presents as a right-sided, T2weighted hyperintense elongate pear-shaped structure on the inferior surface of the liver and is constantly demonstrated from 18 GW onward. The hyperintense signal of fetal bile usually corresponds to T1-weighted hypointensity, but may frequently become iso or hyperintense to liver after 30 GW [70]. The biliary ducts cannot usually be demonstrated under normal conditions. 6.3. Anomalies of position In cases of left-sided CDH, the gallbladder may be found in the midline (with an intrabdominal liver) or entirely leftsided (with an intrathoracic left hepatic lobe). Apart from situs inversus and heterotaxy syndromes (Fig. 17), left-sided gallbladders may also be seen together with variations of the umbilical veins [71], and may be associated with other

Fig. 12. (a) Axial T2-weighted image of a fetus (32 GW) with cardiac failure shows stasis of intrahepatic vessels, and no-flow void. (b) Normal findings in an age-matched control.

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to cease its extension. In the 24th GW, the white pulp occupies about half the organ volume, which is in contrast to the proportion in the postnatal spleen, where the red pulp makes up more than 80% of the volume [80]. The amount of splenic lymphatic tissue increases steadily before birth and continues, without interruption, postantally [78]. Although commonly referred to as a hematopoietic organ, there is accumulating evidence that no hematopoiesis takes place in the human fetal spleen [80,83–87]. 7.2. Imaging

Fig. 13. Frontal T1-weighted image of fetus (32 GW) with liver cirrhosis due to fetal hemochromatosis. Absence of T1-weighted hyperintense signal of the fetal liver. Compare to Fig. 1d.

anomalies [72]. Non-visualization of the gallbladder may be due to contraction of the organ or its absence. Other anomalies include septated or duplicated gallbladders [72], as well as the presence of fetal gallstones [73]. Choledochus cysts present as subhepatic cystic masses with T2-weighted hyperintensity and typical topographical relationships [74–76].

7. Spleen 7.1. Anatomy During the second and third trimester, the human spleen grows allometrically [77], with a steadily increasing mean weight from 27 GW to term [54,78,79]. The characteristic organ structure becomes established between 14 and 24 GW. Splenic lobules begin to form during the 15th to 17th GW [80], differentiation into red and white pulp takes place between 13 and 19 GW [81,82], and accumulations of lymphocytes around the central arteries are recognized by 19–20 GW [80]. Between 20 and 24 GW, the white pulp extends continuously. During this time, a remarkable growth of the lymphatic tissue can be observed, while the red pulp seems

With MRI, the fetal spleen may be identified by its topography dorsal and lateral to the stomach. Despite its small size, the spleen may be detected by 20 GW. The splenic parenchyma shows homogenous signal intensity, which is reported to be similar to that of the liver [3,16,88] (Fig. 14). However, this depends on the sequence used as well as the sequence parameters. In general, no differences in hepatic tissue will be seen on heavily T2-weighted sequences. Steadystate free-precession sequences likewise show little signal differences from those of the liver. Up to 21 GW, little signal differences exist between spleen and liver on both T1- and T2-weighted sequences. Although the signal properties of splenic tissue are subject to some variation, the spleen usually displays less T1- and T2-weighted signal intensity than does the liver in the subsequent GWs. Fig. 14 shows the increase in spleen size, which is accompanied by a small decrease in signal intensity, athough the spleen usually appears a little brighter than the liver, even close to term. Echoplanar sequences reveal marked signal differences between hepatic and splenic tissues up to 28–30 GW, underlining the non-hematopoietic nature of the human fetal spleen (Fig. 15). This hyperintense signal may also relate to the large amounts of white pulp present in the fetal spleen up to 24–28 GW. The remarkable decrease in signal intensity in the subsequent weeks may reflect the increasing red pulp volume during later fetal life. The hypointense appearance of the neonatal spleen relative to liver on both T1- and T2-weighted sequences, as well as subsequent signal changes in the neonatal period, have been attributed to increasing white-pulp-red-pulp ratios [89]. This is not inconsistent with prenatal findings and may be explained by the fact that birth is associated with shrinkage of the whole spleen due to loss of blood from the pulp [78,79], with weight before birth usually regained by four postnatal weeks [78]. 7.3. Anomalies Position: The spleen may be intrathoracic in left-sided CDH together with an intrathoracic, but also with an intraabdominal stomach (Fig. 16). Although connected to the stomach by the gastro-splenic ligament, the position of the spleen is variable, and thus, may be hard to identify, especially in younger fetuses.

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Fig. 14. Axial T2-weighted images through the upper fetal abdomen showing signal intensity of the fetal spleen relative to liver. Fetus at: (a) 25 GW, (b) 33 GW and (c) 39 GW (TE 80 ms). The spleen shows less hypointensity than the liver.

Fig. 15. Sagittal echoplanar images demonstrate signal changes of the fetal spleen and liver: (a) 22 GW, (b) 24 GW, (c) 27 GW and (d) 34 GW. After 24 GW, the fetal spleen becomes increasingly hypointense, which may be explained by the increase in red pulp.

Anomalies in number are found in heterotaxy syndromes [50]. Polysplenia is usually present in left-sided isomerism (Fig. 17). The number of multiple spleens located at the greater curvature of the stomach may vary from two to nine. The splenic masses are of relatively equal size and their combined weight is normal [90]. An absent spleen is characteristic of right-sided isomerism (Ivemark syndrome), and associated with a nearly midline small stomach. Fetal splenomegaly may be seen in anemia due to Rhalloimmunization [91], myeloproliferative disorders [92], or intrauterine infection [93].

8. Pancreas 8.1. Anatomy

Fig. 16. Fetus at 33 GW with left-sided CDH and intraabdominal stomach. Axial T2-weighted image demonstrates right-sided intrathoracic spleen (*).

The fetal pancreas shows the same topographical relationships as those present in the adult [94] and its growth during the second and third trimester correlates well with age [94–96]. During the fetal period, the human exocrine pancreas starts to develop during the 3rd month when acini begin to appear [97,98]. Significant numbers of zymogen granules appear in the fifth fetal month [98,99], when a complex acinar structure becomes evident [100]. From the 25th

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8.2. Imaging The fetal pancreas shows signal intensities similar to adults. It displays intermediate intensity on T2-weighted sequences (like exocrine glands, e.g., the parotid) and appears inhomogeneous (Fig. 18). On T1-weighted sequences, fetal pancreatic tissue shows a hyperintensity comparable to that of the liver (Fig. 18b). With fetal MRI, the pancreas may be identified by its topography, and is ideally depicted when the fluid-filled C-loop of duodenum frames the pancreatic head. Detection of the fetal pancreas with prenatal ultrasound is gestational age-dependent [103], with higher detection rates reported at 20–23 GW than at 36–38 GW [96]. Comparable data are not yet available for prenatal MRI. 8.3. Anomalies Apart from the very rare congenital cysts of the pancreas that appear as T2-weighted hyperintense cystic lesions dorsal to the stomach [16], the only relevant anomaly is the annular pancreas, which is frequently associated with, or may lead to, duodenal obstruction [18].

Fig. 17. Fetus at 28 GW with heterotaxy syndrome (left-sided isomerism) and abdominal situs inversus. Axial T2-weighted image demonstrates polysplenia with at least three spleens (arrowheads). Note also nearly median-positioned gallbladder (arrow).

GW to term, the lobular arrangement becomes more accentuated and acinar cell volume increases steadily [101]. With the exception of amylase, pancreatic enzymes are detectable from 15 GW onward, with no lipase present before 21 GW [100,101]. Development of the endocrine pancreas starts shortly before the exocrine pancreas, when islets of Langerhans can be detected [97]. The human endocrine pancreas shows its highest growth rate between 21 and 40 GW [102].

9. Adrenal glands 9.1. Anatomy In contrast to the adult, adrenal glands are relatively large organs in the fetus. During the second and third trimester, there is a marked increase in size [104,105], with the left adrenal significantly heavier than the right for the same gestational age [104]. At birth, the adrenals have adult dimensions, weighing 5 g each [106], but show marked involution within the first four postnatal months [106]. The remarkable increase in size of the fetal adrenal glands is mainly due to the presence of a well-developed inner zone of the adrenal cortex (so-called “fetal zone”), which involutes after birth [107,108]. At term, this zone compromises about

Fig. 18. (a) Axial T2-weighted image at 27 GW. Pancreas is seen from its head to its tail. Pancreatic tissue has moderately hypointense signal characteristics, comparable to spleen and liver. (b) Sagittal T1-weighted image (23 GW): arrow points to the hyperintense pancreatic body dorsal to the stomach.

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Fig. 19. (a) Fetus at 21 GW, frontal T2-weighted image. The suprarenal glands show a trifoliate configuration with central hyperintensity. (b) Frontal T1-weighted image (27 GW): homogenous hyperintensity of adrenal glands. (c) Fetus at 35 GW, frontal T2-weighted image (TE 80): adrenal glands have homogenous signal intensity similar to spleen.

80% of the fetal adrenal cortex [107,108], or 85% of the total organ volume [106], but involutes within the first 4 months after birth [106,108]. Growth of the adrenals depends on an intact hypothalamicpituitary-adrenal axis, as evidenced by the small adrenals seen in anencephalic fetuses [107,109,110]. In early fetal stages, the fetal adrenal does not have a medulla as a distinct entity; medullary cells are scattered in small clumps and make up only 1% of the total gland volume [111]. The volume of the adrenal medulla increases slowly up to 20 GW and, subsequently, grows more rapidly until 31 GW [112]. This enlargement is mainly due to the developing capillary sinusoids and proliferation of the medullary cells. In older fetuses, sinusoids make up about 36% of the medullary volume [112]. Medullary maturation continues during postnatal life, but it is not until 12–18 months of age that the infant has a medulla with the adult type architecture. 9.2. Imaging With fetal MRI, the adrenal glands are already recognizable by 20 GW, as they present with marked hypointense signals on T2-weighted sequences (Fig. 19) and are demarcated from the adjacent organs by the hyperintense perirenal adipose tissues. Adrenals are best depicted on T2-weighted sequences, as steady-state free-precession sequences do not provide enough contrast (in younger fetuses). By that time, the adrenal glands show T2-weighted hypointensity in the periphery and – depending on the section plane – a central hypertensity (Fig. 19a). However, the latter does not represent the adrenal medulla, since the medulla only makes up about 1% of the fetal gland by that time [111] and, therefore, cannot be visualized. The central hyperintensity should be considered to represent the inner parts of the fetal zone, while

the peripheral hypointense region comprises both the outer fetal and definitive cortex. Such differentiation is not possible with T1-weighted sequences, where the whole organ shows a hyperintense signal similar to that of the liver (Fig. 19b). After 35 GW, however, T2-weighted signal intensity decreases and the glands are less conspicuous (Fig. 19c), showing a signal intensity similar to the spleen. Thus, the right adrenal is better demarcated from the more hypointense-appearing liver. 9.3. Anomalies The absence of one adrenal gland has been reported to be a common condition in cases of unilateral renal agenesis [113]. In cases of bilateral renal agenesis or ectopic kidney, the adrenals appear enlarged and more globular or discoidshaped [114]. Enlargement of the adrenal glands is seen in congenital adrenal hyperplasia [115], but, to date, the MR appearance of this condition is unknown. Cystic adrenal masses in the fetus include simple cysts, antenatal hemorrhage, and cystic neuroblastoma [116]. With fetal MRI, congenital cystic neuroblastomas present as intracystic septations, extensive areas of hemorrhage and necrosis [117], and increased intracystic fluid levels [118]. Fetal MRI is thought to provide a better differential diagnosis of neuroblastoma from conditions such as adrenal hemorrhage, subdiaphragmatic sequestration, or renal cortical cysts [117], and retroperitoneal lymphangioma [119]. However, solid neuroblastomas have also been reported, presenting with intermediate signal intensity on T2-weighted images [120]. 10. Conclusion The MR appearance of the fetal abdomen varies with gestational age and the ability to visualize and differenti-

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ate specific structures depends on the size of the structure, as well as the signal characteristics of the structure on various sequences. Gestational age is an important factor in depicting abdominal anatomy. Indeed, more details can be observed when the fetus is larger. Knowledge of normal development is crucial to understand and interpret fetal MR images. In fetal abdominal MRI, one must use a variety of sequences (and combinations of sequences) to properly assess normal and pathologic fetal anatomy, and to cover various aspects of organ-specific function, which, in part, can be visualized with fetal MRI. Many organs pass through characteristic developmental stages that are mirrored by changes in their signal characteristics. Although fetal abdominal imaging is still an emerging technique, it opens a wide and promising field of investigation.

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