- Email: [email protected]
Prenatal magnetic resonance imaging enhances fetal diagnosis
Prenatal Magnetic Resonance Imaging Enhances Fetal Diagnosis By Theresa
M. Quinn,
Anne
M.
Philadelphia,
6ackground:Ultrasound (US) evaluation of some fetal anomalies provides limited information. Anatomic details that affect prognosis and selection for fetal therapy, such as liver herniation and pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) and airway patency in giant neck masses, may be difficult to delineate using conventional sonographic methods. The authors evaluated the utility of prenatal magnetic resonance imaging (MRI) with new ultrafast imaging sequences in the diagnosis and management of fetal anomalies. Methods: From April 1996 to April 1997 45 MRI scans were performed in 31 pregnant women with an US diagnosis of a fetal anomaly. The US diagnoses included CDH, giant neck masses, lung masses, abdominal and pelvic abnormalities, twin anomalies, and central nervous system (CNS) anomalies. The fetuses ranged in age from 18 to 39 weeks’ gestation (mean, 28.7 weeks). Using a 1.5-T magnet, a variety of ultrafast imaging sequences were performed including fast gradient-echo, half-fourier single shot turbo spin-echo (Haste) and echo-planar imaging yielding images with T, to T2 type weighting. Results: With CDH, MRI demonstrated liver herniation into the chest in 11 of 14 cases. In four cases, US findings had not been definitive. In two cases of CDH detected by MRI, the primary diagnosis by US had been congenital cystic adeno-
T
HE PRENATAL DIAGNOSIS of fetal malformations provides insight into pathophysiology and facilitates patient management. The advent of high resolution ultrasound (US) and color flow Doppler imaging has revolutionized prenatal diagnosis for most anomalies. 1.2 Despite advances in sonography, the prenatal diagnosis of anomalies like congenital diaphragmatic hernia (CDH) is difficult and has been missed in 41% of cases in one recent retrospective study.3 In prenatally diagnosed left CDH, the sonographic predictors for poor outcome include a low right lung area to head circumference ratio (LHR) and herniation of liver into the thorax.4 The ability to diagnose CDH and the position of the liver with US depends on the skill of the examiner. Differentiating between chest masses such as congenital cystic adenomatoid malformation (CCAM) and bronchopulmonary sequestration (BPS) by US can be difficult. Radiological evaluation of airway compromise by large fetal neck masses can affect perinatal management. We evaluated the utility of prenatal magnetic resonance imaging (MRI) with new ultrafast imaging sequences in the diagnosis and management of fetal anomalies. Journal
of Pediatric
Surgery,
Vol33,
No 4 (April),
1998: pp 553-558
Hubbard,
and
N. Scott
Adzick
Pennsylvania
matoid malformation (CCAM). With lung masses, MRI accurately distinguished between CCAM and bronchopulmonary sequestration (BPS). For giant neck masses with potential airway obstruction, MRI scans permitted differentiation of teratoma from cystic hygroma and allowed delineation of fetal airway involvement. The accurate anatomic evaluation facilitated planning for the ex utero intrapartum treatment (EXIT) procedure, a technique for securing the airway while the term fetus is still on placental support. With huge abdominal masses such as enterogenous cyst and lymphangioma, MRI scanning clarified the diagnosis. Fourteen of the 31 (45%) patients underwent fetal treatment after US and MRI evaluation. Conclusions: Prenatal MRI enhances fetal anatomic evaluation and facilitates perinatal management and family counseling. Ultrafast imaging sequence MRI is helpful to corroborate and refine US diagnoses. Fetal MRI is a valuable adjunct to US for prenatal diagnosis before fetal surgical intervention for selected life-threatening birth defects. J Pediatr Surg 33:553-558. Copyright o 1998 by W.B. Saunders Company. INDEX WORDS: Magnetic resonance imaging, fetal diaphragmatic hernia, prenatal diagnosis, fetal therapy, ultrasonography, fetal anomalies, fetal thoracic masses, twin anomalies.
MATERIALS
AND
METHODS
Between April 1996 and April 1997 over 200 women were referred to The Center for Fetal Diagnosis and Treatment at The Children’s Hospital of Philadelphia after an US examination had identified a fetal anomaly. Thirty-one of the women were referred for MRI. The patients selected for fetal MRI scanning were fetal surgery candidates undergoing a multidisciplinary evaluation for a congenital anomaly that was a potentially correctable lesion or a diagnostic dilemma. A repeat US for complete fetal examination was performed using an ATL HDI 3000 ultrasound machine (Bothell, Washington). The diagnoses included CDH (n = 14), lung masses (n = 4), giant neck masses (n = 3), abdominal and pelvic abnormalities (n = 4), twin anomalies (n = 2),
From the Center for Fetal Diagnosis and Treatment, The Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, PA. Presented at the 28th Annual Meeting of the American Pediatric Surgical Association, Naples, Florida, May 17.21, 1997. This study was supported in part by the C. Everett Coop Endowed Chai,: Address reprint requests to N. Scott Adzick, MD, The Centerfor Fetal Diagnosis and Treatment, The Children’s Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA 19104. Copyright 0 1998 by WB. Saunders Company 0022-3468/98/3304-0002$03.00/O 553
554
QUINN,
HUBBARD,
AND
ADZICK
and central nervous system (CNS) anomalies (n = 4). The results of the US examination were known at the time of the MRI study. Informed consent was obtained from the mother. On the same day as the US examination, MRI was performed in a Siemens 1.5 T Vision Magnetom (Siemens Medical Systems, Erlangen, Germany) using a phased array body coil. The imaging sequences included a variety of ultrafast imaging sequences: fast gradient-echo, half-fourier single shot turbo spin-echo (Haste), and echo-planar images. The images were obtained in transverse, sagittal, and coronal planes with a field of view large enough to include the entire maternal abdomen and pelvis to prevent problems with aliasing. Forty-five examinations were performed, with serial scans in several patients to follow the anomaly over time. The examinations were performed without sedation of the mother or the fetus and lasted 30 to 40 minutes. The scans were evaluated by one radiologist (AMH). All diagnoses were confirmed after delivery by radiographic imaging, operation, or autopsy.
RESULTS
Fetal MRI for CDH provided detail that refined the anatomic diagnosis in all 14 cases. The information included the amount and location of bowel, stomach, and liver herniated into the fetal thorax (Fig 1). The degree of liver hemiation was substantial in six cases in which a third or more of the fetal liver was intrathoracic, in some instances extending to the apex of the thorax. MRI demonstrated liver hemiation into the chest in 11 of 14
Fig 2. A 27-week-old fetus with BPS. Axial Haste image through the chest at the level of the four-chamber view of the heart (curved arrow) shows a high signal intensity lesion (large straight arrow) in the posterior aspect of the right lung. The lesion is easily differentiatedfrom the remaining normal right lung (small straight arrow).
Fig 1. A 2B-week-old fetus with left CDH. Sagittal Haste image through the fetus shows large amount of liver (arrowheads) extending into the left thorax. The portal vessels (open arrow) can be seen coursing up into chest. Also note the high intensity stomach (black arrow) herniated into the chest with the liver and the small amount of compressed residual lung (white arrow).
cases. In four cases US findings had not been definitive. In two cases of CDH detected by MRI the primary diagnosis by US had been CCAM. In the early part of our experience, MRI failed to identify liver herniation in one case of CDH that was also missed by US. MRI was able to identify abnormalities that had been poorly defined or missed by US, such as bilateral CDH in one fetus, and to exclude other diagnoses, such as a suspected DandyWalker malformation in another case. As with CDH, fetal MRI provided more anatomic detail than US regarding the extent and location of the chest masses that included BPS (n = 2) and CCAM (n = 2). In many cases the lobe of the lung involved with the lesion could be identified. MRI was able to distinguish BPS from CCAM (Figs 2 and 3). One BPS that had “disappeared” on US by 27 weeks’ gestation, but remained easily detectable by MRI, resulted in respiratory distress in the neonatal period and required resection shortly after birth. MRI could identify normal fetal lung reliably. In one patient who underwent resection of a huge left lower lobe CCAM in a hydropic fetus at 22 weeks’ gestation, serial postoperative MRI scans demonstrated significant lung growth. She was delivered at 35 weeks’ gestation and required no ventilatory support.
PRENATAL
MRI ENHANCES
FETAL
DIAGNOSIS
555
Fig 3. A 28~week-old fetus with CCAM. Axial Haste images through the fetus. (A) Image through the chest at the level of the four-chamber view of the heart (small straight arrow) shows marked deviation of the heart into the left hemithorax. In the right hemithorax there is a large lesion with multiple areas of high signal intensity consistent with cysts (short broad arrows). Remaining right lung (curved arrow1 can be seen displaced into the left chest. There is severe compression of the left lung (open arrow). (B) Image through the upper abdomen shows the liver (large white arrow) surrounded by a massive amount of ascitic fluid (small black arrows). Posteriorly, the kidneys are seen (small white arrows). Hydrops had developed in the fetus from compression of the heart and great vessels by the large CCAM.
Fetal MRI was instrumental in evaluating the anatomic extent of giant neck masses. The lesions included cystic teratoma and cystic hygroma. In contrast to US, anatomic details about the location and impingement of the fetal airway and neck vessels by lesions that rivaled the fetus in volume were better seen with MRI. Cervical teratoma was differentiated from cystic hygroma. In each case, fetal MRI aided in the prenatal assessment of the mass before cesarean delivery using an ex utero intrapartum therapy (EXIT) procedure to establish an airway.5,6 The abdominal and pelvic abnormalities evaluated
Fig 4. A 24-week-old fetus with a sacrococcygeal teratoma. IA) Sagittal Haste image through the entire fetus demonstrates a large exophytic tumor (small arrows), a third of which extends into the fetal pelvis. The urinary bladder (open arrow) is distended and displaced out of the pelvis. (B) Coronal Haste image through the fetus demonstrates the exophytic portion of the tumor (small arrows) and a dilated, thickwalled bladder (open arrow). No metastases were detected in the liver (short broad arrow).
included sacrococcygeal teratoma (SCT), lymphangioma, giant omphalocele, and enterogenous cyst. The extent of the tumors and cysts was accurately assessedby MRI. MRI provided anatomic localization and tissue differentiation that were helpful in defining the diagnosis. For SCT, the intrapelvic extent of tumor was nicely demonstrated (Fig 4). The extent of the abdominal wall defect and contents of a giant omphalocele were accurately assessed by MRI. Finally, the diagnostic dilemma of a huge cyst extending the length of the thorax, abdomen, and pelvis, previously diagnosed by US as a
556
cystic hygroma or CCAM, was accurately diagnosed to be a massive foregut malformation by MRI. The CNS abnormalities evaluated by MRI included arteriovenous malformations, aqueductal stenosis, agenesis of the corpus callosum, and caudal regression. MRI was instrumental for evaluating the extent of vascular lesions and the amount of parenchymal preservation around the lesion (Fig 5). MRI was able to exclude a suspected Dandy-Walker malformation in a fetus with agenesis of the corpus callosum. When assessing twin anomalies by US, the problems of multiple fetuses in the field, fetal lie, and aberrant anatomy can create diagnostic confusion. The field of view provided by MRI allowed anatomic refinement of the US diagnoses of Acardia-acephalus twins and twintwin transfusion syndrome. In particular, the placental anatomy and cord insertion sites were delineated for diagnosis and preoperative planning for cord ligation or placental vessel laser ablation. There were some notable difficulties with the technique of MRI in this series. Three patients became claustrophobic, were unable to tolerate the scan, and were not included in the study. With polyhydramnios or very young fetuses (18 to 20 weeks), there was increased fetal
Fig 5. A 30-week-old twin gestation with Vein of Galen arteriovenous malformation. Sagittal Haste through the maternal uterus demonstrates a coronal image of the normal twin brain (short broad arrow). An off-axis axial image through the brain in the abnormal twin demonstrates marked enlargement of the lateral ventricles (black open arrows). The dilated straight sinus (open white arrow) is seen in the midline. There was severe cortical atrophy. The amnion (small black arrow) can be seen separating the diamniotic twins.
QUINN,
HUBBARD,
AND
ADZICK
motion with reduction in the quality of the scan. In addition, maternal obesity required a larger field of view that resulted in decreased fetal detail. However, the problems with fetal motion and maternal obesity did not prevent the identification of the anatomic malformation. DISCUSSION
We evaluated the usefulness of fetal MRI with ultrafast imaging sequences in the diagnosis and management of selected fetal anomalies referred to our center over the course of 1 year. Patients undergoing fetal MRI were surgery candidates undergoing a multidisciplinary evaluation for a congenital anomaly that was a potentially correctable lesion or a diagnostic dilemma. Although MRI using standard spin-echo sequences has been used in the past to determine fetal anatomy, fetal motion severely limited the quality and diagnostic utility of the scans. Maternal sedation or fetal paralysis were necessary to obtain useful images using these slower sequences? Our study used ultrafast MRI sequences that included fast gradient echo (less than 30-second acquisition time), half fourier single-shot turbo spin-echo sequences (Haste), and echo planar sequences (EPI) in which the anatomic sections are acquired sequentially, each in less than 1 second, thereby decreasing motion artifacts8 Although the diagnostic possibilities of fetal MRI are exciting, it is important to consider safety issues for the implementation of this new technique. All of the sequences used in this study are approved by the FDA and are considered safe. One long-term study evaluated 20 children who had undergone fetal MRI with EPI sequences between 21 weeks’ gestation and term. After 3 years follow-up there were no deleterious effects from fetal MR19 A survey of 1,915 pregnant MRI nurses and technicians showed no increase in the rate of fetal loss or anomalies compared with the general populationLO However, the study addressed the effect of working in a high static magnetic field and not the issues of the radiofrequency electromagnetic fields that occur in the bore of the magnet. These reviews are reassuring, but studies using high-strength MR in chick embryos have shown some teratologic effects. l1 Thus, we have limited our studies in the following fashion to reduce possible risks: (1) restriction of fetal MRI examinations to patients beyond 18 weeks’ gestation to minimize a possible teratologic effect; (2) although the Haste sequences have multiple inversion pulses that can theoretically increase the energy and heat deposited into the patient, the flip angles were decreased from the usual 180” to 120”, thereby significantly reducing the amount of energy depositions and (3) the studies were designed to obtain as much information with the fewest number of sequences possible. With recent advances in prenatal US diagnosis, CDH is
PRENATAL
MRI ENHANCES
FETAL
557
DIAGNOSIS
frequently diagnosed before birth. The mortality in CDH relates to the degree of pulmonary hypoplasia and associated pulmonary hypertension and has been estimated to be as high as 58%.12 Identifying possible predictors of decreased survival in CDH, including estimations of the residual lung area and determination of liver hemiation, is not always possible by ultrasound scan.4J3Identification of these features is highly dependent on the skill of the examiner. With MRI using ultrafast sequences there was excellent tissue contrast with greater tissue differentiation than that obtained with US. In particular, the fetal lungs were easily seen by MRI using Haste sequences. The fetal stomach, liver, and various mass lesions were also well visualized with this technique. Both the identity of the tissue and an estimation of the amount present in the chest could be assessed with MRI. Because the presence of herniated fetal liver within the fetal chest is a predictor of poor neonatal outcome and the position of the fetal liver may also affect selection of patients for fetal intervention for CDH using temporary tracheal occlusion, this information was helpful for counseling families. While some fetal lung masses regress spontaneously, some masses enlarge, compressing the residual lung causing pulmonary hypoplasia. These lesions can progress to compromise the vena cava and heart leading to fetal hydrops and death. I4 Although US is effective at assessing hydrops, estimating the degree of hypoplasia has been unsuccessful to date. We found MRI to be particularly effective at identifying the amount of residual fetal lung and differentiating it from chest masses. Two cases referred to us involved CDH mistaken for CCAM based on the presence of nonperistaltic bowel in the chest that may appear as a multicystic lesion similar to a CCAM on US. The MRI characteristics of gut are very different from that of lung and lung tumors, allowing their clear differentiation. Although we were able to differentiate between CCAM and BPS by MRI in this study, the distinction between the two can also be made by color flow Doppler US based on identification of a feeding systemic artery to the BPS.15 Although lung volumes were measured in all CDH and chest lesion cases, the experience is still too limited to draw conclusions regarding the extent of pulmonary hypoplasia. The ability to identify normal lung and evaluate lung volume may be crucial to assessthe degree of pulmonary hypoplasia in CDH, compressive lung masses, and giant omphalocele. As MRI technique is
refined and normal lung volume estimates determined, predictions of pulmonary hypoplasia may be possible. The large field of view provided by MRI contributed to the accurate diagnosis of very large fetal lesions in the neck and the abdomen. Compared with ultrasound examinations in which only a small part of the lesion may be present in the acoustic window, the whole lesion and its anatomic relations could be viewed on the MRI sections. The information about the impingement of the fetal airway and neck vessels by huge cervical masses was better delineated by MRI than by US and was crucial for planning the EXIT procedure, a technique for securing the airway in a fetus while placental perfusion is maintained.5,6 Conventional postnatal airway management may have precluded the survival of all of these patients for whom airway accessvia endotracheal tube placement or tracheostomy required up to 55 minutes of placental bypass. Cervical teratoma was differentiated from cystic hygroma by MRI. The anatomic information allowed appropriate family counseling for the likelihood of survival and extent of disability in these fetuses with masses that were often nearly the size of the fetus itself. MRI confers a clear advantage in the evaluation of the fetal brain. Normal gyral patterns, ventricular size, and patterns of neuronal migration have all been documented by MRI.16 The posterior fossa is best evaluated by MRI, with significant detail of the cerebellar vermis possible to confirm or exclude Dandy-Walker malformation, a difficult diagnosis to make -accurately by US.17 MRI is superior to ultrasonography for the purpose of excluding CNS anomalies in a fetus with a malformation that may be amenable to fetal therapy. Although US remains the standard for prenatal diagnosis and screening, the quality of the examination is dependent on the availability of high-quality ultrasound equipment and a skilled examiner. Prenatal MRI using ultrafast sequences is still in its infancy. However, in our prospective study we found MRI using ultrafast imaging sequences provides superior tissue contrast and a variety of imaging planes regardless of the fetal lie. Prenatal MRI is particularly helpful at improving the anatomic definition, clarifying the diagnosis, and identifying other associated abnormalities. Fetal MRI is a valuable adjunct to the evaluation of an abnormal fetus. ACKNOWLEDGMENT The authors acknowledge preparation of the manuscript.
the help of Lori
Howell,
RN, MS, in the
REFERENCES 1. D’Alton ME, DeChemey AH: Prenatal diagnosis. N Engl J Med 328:114-120, 1993 2. Garmel SH, D’ Alton ME: Diagnostic ultrasound in pregnancy: An overview. Semin Perinatol 18:117-132, 1994
3. Lewis DA, Reichart C. Bowerman R, et al: Prenatal ultrasound frequently fails to diagnose congenital diaphragmatic hernia. J Pediatr Surg 32:352-356, 1997 4. Metkus AP Filly RA, Stringer MD, et al: Sonographic predictors
QUINN,
of survival in fetal diaphragmatic hernia. J Pediatr Surg 31:148-152, 1996 5. Mychaliska GB, Bealer JF, Graf JL, et al: Operating on placental support: The Ex Utero Intrapartum Treatment (EXIT) procedure. J Pediatr Surg 32:227-231, 1997 6. Crombleholme TM, Hubbard AM, Howell LJ, et al: EXIT Procedure (Ex Utero Intrapartum Treatment) for giant fetal neck masses. Am J Obstet Gynecol 176S84, 1997 7. Weinreb JC, Lowe T, Cohen JM, et al: Human fetal anatomy. Radiology 157:715-720, 1985 8. Semelka RC, Kelekis NL, Thomason D, et al: HASTE MR imaging: Description of technique and preliminary results in the abdomen. J Magn Reson Imaging 6:698-699, 1996 9. Baker PN, Johnson DM, Harvey PR, et al: A three year follow-up of children imaged in utero with echo-planar magnetic resonance. Am J Obstet Gynecol 170:32-33, 1994 10. Kanal E, Gillen J, Evans JA, et al: Survey of reproductive health among female MR workers. Radiology 187:395-399, 1993
HUBBARD,
AND
ADZICK
11. Yip YP, Capriotti C, Talagala SL, et al: Effects of MR exposure at 1.5T on early embryonic development of the chick. J Magn Reson Imaging 4:742-748, 1994 12. Harrison MR, Adzick NS, Estes JM, et al: A prospective study of the outcome for fetuses with diaphragmatic hernia. JAMA 271:382-384, 1994 13. Bootstaylor BS, Filly RA, Harrison MR, et al: Prenatal sonographic predictors of liver hemiation in congenital diaphragmatic hernia. J Ultrasound Med 14:515-520,1995 14. Adzick NS, Harrison MR: Fetal surgical therapy. Lancet 343:897902, 1994 15. MacGillivray TE, Harrison MR, Goldstein RB, et al: Disappearing fetal lung lesions. J Pediatr Surg 28:1321-1325, 1993 16. Naidich TP, Grant IL, Altman N, et al: The developing cerebral surface. Neurosurg Clin North Am 4:201-240, 1994 17. Filly RA: Ultrasound evaluation of the fetal neural axis, in Callen PW (ed): Ultrasonography in Obstetrics and Gynecology, New York, NY, WB Saunders, 1994, pp 189-234
M. Quinn,
Anne
M.
Philadelphia,
6ackground:Ultrasound (US) evaluation of some fetal anomalies provides limited information. Anatomic details that affect prognosis and selection for fetal therapy, such as liver herniation and pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) and airway patency in giant neck masses, may be difficult to delineate using conventional sonographic methods. The authors evaluated the utility of prenatal magnetic resonance imaging (MRI) with new ultrafast imaging sequences in the diagnosis and management of fetal anomalies. Methods: From April 1996 to April 1997 45 MRI scans were performed in 31 pregnant women with an US diagnosis of a fetal anomaly. The US diagnoses included CDH, giant neck masses, lung masses, abdominal and pelvic abnormalities, twin anomalies, and central nervous system (CNS) anomalies. The fetuses ranged in age from 18 to 39 weeks’ gestation (mean, 28.7 weeks). Using a 1.5-T magnet, a variety of ultrafast imaging sequences were performed including fast gradient-echo, half-fourier single shot turbo spin-echo (Haste) and echo-planar imaging yielding images with T, to T2 type weighting. Results: With CDH, MRI demonstrated liver herniation into the chest in 11 of 14 cases. In four cases, US findings had not been definitive. In two cases of CDH detected by MRI, the primary diagnosis by US had been congenital cystic adeno-
T
HE PRENATAL DIAGNOSIS of fetal malformations provides insight into pathophysiology and facilitates patient management. The advent of high resolution ultrasound (US) and color flow Doppler imaging has revolutionized prenatal diagnosis for most anomalies. 1.2 Despite advances in sonography, the prenatal diagnosis of anomalies like congenital diaphragmatic hernia (CDH) is difficult and has been missed in 41% of cases in one recent retrospective study.3 In prenatally diagnosed left CDH, the sonographic predictors for poor outcome include a low right lung area to head circumference ratio (LHR) and herniation of liver into the thorax.4 The ability to diagnose CDH and the position of the liver with US depends on the skill of the examiner. Differentiating between chest masses such as congenital cystic adenomatoid malformation (CCAM) and bronchopulmonary sequestration (BPS) by US can be difficult. Radiological evaluation of airway compromise by large fetal neck masses can affect perinatal management. We evaluated the utility of prenatal magnetic resonance imaging (MRI) with new ultrafast imaging sequences in the diagnosis and management of fetal anomalies. Journal
of Pediatric
Surgery,
Vol33,
No 4 (April),
1998: pp 553-558
Hubbard,
and
N. Scott
Adzick
Pennsylvania
matoid malformation (CCAM). With lung masses, MRI accurately distinguished between CCAM and bronchopulmonary sequestration (BPS). For giant neck masses with potential airway obstruction, MRI scans permitted differentiation of teratoma from cystic hygroma and allowed delineation of fetal airway involvement. The accurate anatomic evaluation facilitated planning for the ex utero intrapartum treatment (EXIT) procedure, a technique for securing the airway while the term fetus is still on placental support. With huge abdominal masses such as enterogenous cyst and lymphangioma, MRI scanning clarified the diagnosis. Fourteen of the 31 (45%) patients underwent fetal treatment after US and MRI evaluation. Conclusions: Prenatal MRI enhances fetal anatomic evaluation and facilitates perinatal management and family counseling. Ultrafast imaging sequence MRI is helpful to corroborate and refine US diagnoses. Fetal MRI is a valuable adjunct to US for prenatal diagnosis before fetal surgical intervention for selected life-threatening birth defects. J Pediatr Surg 33:553-558. Copyright o 1998 by W.B. Saunders Company. INDEX WORDS: Magnetic resonance imaging, fetal diaphragmatic hernia, prenatal diagnosis, fetal therapy, ultrasonography, fetal anomalies, fetal thoracic masses, twin anomalies.
MATERIALS
AND
METHODS
Between April 1996 and April 1997 over 200 women were referred to The Center for Fetal Diagnosis and Treatment at The Children’s Hospital of Philadelphia after an US examination had identified a fetal anomaly. Thirty-one of the women were referred for MRI. The patients selected for fetal MRI scanning were fetal surgery candidates undergoing a multidisciplinary evaluation for a congenital anomaly that was a potentially correctable lesion or a diagnostic dilemma. A repeat US for complete fetal examination was performed using an ATL HDI 3000 ultrasound machine (Bothell, Washington). The diagnoses included CDH (n = 14), lung masses (n = 4), giant neck masses (n = 3), abdominal and pelvic abnormalities (n = 4), twin anomalies (n = 2),
From the Center for Fetal Diagnosis and Treatment, The Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, PA. Presented at the 28th Annual Meeting of the American Pediatric Surgical Association, Naples, Florida, May 17.21, 1997. This study was supported in part by the C. Everett Coop Endowed Chai,: Address reprint requests to N. Scott Adzick, MD, The Centerfor Fetal Diagnosis and Treatment, The Children’s Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA 19104. Copyright 0 1998 by WB. Saunders Company 0022-3468/98/3304-0002$03.00/O 553
554
QUINN,
HUBBARD,
AND
ADZICK
and central nervous system (CNS) anomalies (n = 4). The results of the US examination were known at the time of the MRI study. Informed consent was obtained from the mother. On the same day as the US examination, MRI was performed in a Siemens 1.5 T Vision Magnetom (Siemens Medical Systems, Erlangen, Germany) using a phased array body coil. The imaging sequences included a variety of ultrafast imaging sequences: fast gradient-echo, half-fourier single shot turbo spin-echo (Haste), and echo-planar images. The images were obtained in transverse, sagittal, and coronal planes with a field of view large enough to include the entire maternal abdomen and pelvis to prevent problems with aliasing. Forty-five examinations were performed, with serial scans in several patients to follow the anomaly over time. The examinations were performed without sedation of the mother or the fetus and lasted 30 to 40 minutes. The scans were evaluated by one radiologist (AMH). All diagnoses were confirmed after delivery by radiographic imaging, operation, or autopsy.
RESULTS
Fetal MRI for CDH provided detail that refined the anatomic diagnosis in all 14 cases. The information included the amount and location of bowel, stomach, and liver herniated into the fetal thorax (Fig 1). The degree of liver hemiation was substantial in six cases in which a third or more of the fetal liver was intrathoracic, in some instances extending to the apex of the thorax. MRI demonstrated liver hemiation into the chest in 11 of 14
Fig 2. A 27-week-old fetus with BPS. Axial Haste image through the chest at the level of the four-chamber view of the heart (curved arrow) shows a high signal intensity lesion (large straight arrow) in the posterior aspect of the right lung. The lesion is easily differentiatedfrom the remaining normal right lung (small straight arrow).
Fig 1. A 2B-week-old fetus with left CDH. Sagittal Haste image through the fetus shows large amount of liver (arrowheads) extending into the left thorax. The portal vessels (open arrow) can be seen coursing up into chest. Also note the high intensity stomach (black arrow) herniated into the chest with the liver and the small amount of compressed residual lung (white arrow).
cases. In four cases US findings had not been definitive. In two cases of CDH detected by MRI the primary diagnosis by US had been CCAM. In the early part of our experience, MRI failed to identify liver herniation in one case of CDH that was also missed by US. MRI was able to identify abnormalities that had been poorly defined or missed by US, such as bilateral CDH in one fetus, and to exclude other diagnoses, such as a suspected DandyWalker malformation in another case. As with CDH, fetal MRI provided more anatomic detail than US regarding the extent and location of the chest masses that included BPS (n = 2) and CCAM (n = 2). In many cases the lobe of the lung involved with the lesion could be identified. MRI was able to distinguish BPS from CCAM (Figs 2 and 3). One BPS that had “disappeared” on US by 27 weeks’ gestation, but remained easily detectable by MRI, resulted in respiratory distress in the neonatal period and required resection shortly after birth. MRI could identify normal fetal lung reliably. In one patient who underwent resection of a huge left lower lobe CCAM in a hydropic fetus at 22 weeks’ gestation, serial postoperative MRI scans demonstrated significant lung growth. She was delivered at 35 weeks’ gestation and required no ventilatory support.
PRENATAL
MRI ENHANCES
FETAL
DIAGNOSIS
555
Fig 3. A 28~week-old fetus with CCAM. Axial Haste images through the fetus. (A) Image through the chest at the level of the four-chamber view of the heart (small straight arrow) shows marked deviation of the heart into the left hemithorax. In the right hemithorax there is a large lesion with multiple areas of high signal intensity consistent with cysts (short broad arrows). Remaining right lung (curved arrow1 can be seen displaced into the left chest. There is severe compression of the left lung (open arrow). (B) Image through the upper abdomen shows the liver (large white arrow) surrounded by a massive amount of ascitic fluid (small black arrows). Posteriorly, the kidneys are seen (small white arrows). Hydrops had developed in the fetus from compression of the heart and great vessels by the large CCAM.
Fetal MRI was instrumental in evaluating the anatomic extent of giant neck masses. The lesions included cystic teratoma and cystic hygroma. In contrast to US, anatomic details about the location and impingement of the fetal airway and neck vessels by lesions that rivaled the fetus in volume were better seen with MRI. Cervical teratoma was differentiated from cystic hygroma. In each case, fetal MRI aided in the prenatal assessment of the mass before cesarean delivery using an ex utero intrapartum therapy (EXIT) procedure to establish an airway.5,6 The abdominal and pelvic abnormalities evaluated
Fig 4. A 24-week-old fetus with a sacrococcygeal teratoma. IA) Sagittal Haste image through the entire fetus demonstrates a large exophytic tumor (small arrows), a third of which extends into the fetal pelvis. The urinary bladder (open arrow) is distended and displaced out of the pelvis. (B) Coronal Haste image through the fetus demonstrates the exophytic portion of the tumor (small arrows) and a dilated, thickwalled bladder (open arrow). No metastases were detected in the liver (short broad arrow).
included sacrococcygeal teratoma (SCT), lymphangioma, giant omphalocele, and enterogenous cyst. The extent of the tumors and cysts was accurately assessedby MRI. MRI provided anatomic localization and tissue differentiation that were helpful in defining the diagnosis. For SCT, the intrapelvic extent of tumor was nicely demonstrated (Fig 4). The extent of the abdominal wall defect and contents of a giant omphalocele were accurately assessed by MRI. Finally, the diagnostic dilemma of a huge cyst extending the length of the thorax, abdomen, and pelvis, previously diagnosed by US as a
556
cystic hygroma or CCAM, was accurately diagnosed to be a massive foregut malformation by MRI. The CNS abnormalities evaluated by MRI included arteriovenous malformations, aqueductal stenosis, agenesis of the corpus callosum, and caudal regression. MRI was instrumental for evaluating the extent of vascular lesions and the amount of parenchymal preservation around the lesion (Fig 5). MRI was able to exclude a suspected Dandy-Walker malformation in a fetus with agenesis of the corpus callosum. When assessing twin anomalies by US, the problems of multiple fetuses in the field, fetal lie, and aberrant anatomy can create diagnostic confusion. The field of view provided by MRI allowed anatomic refinement of the US diagnoses of Acardia-acephalus twins and twintwin transfusion syndrome. In particular, the placental anatomy and cord insertion sites were delineated for diagnosis and preoperative planning for cord ligation or placental vessel laser ablation. There were some notable difficulties with the technique of MRI in this series. Three patients became claustrophobic, were unable to tolerate the scan, and were not included in the study. With polyhydramnios or very young fetuses (18 to 20 weeks), there was increased fetal
Fig 5. A 30-week-old twin gestation with Vein of Galen arteriovenous malformation. Sagittal Haste through the maternal uterus demonstrates a coronal image of the normal twin brain (short broad arrow). An off-axis axial image through the brain in the abnormal twin demonstrates marked enlargement of the lateral ventricles (black open arrows). The dilated straight sinus (open white arrow) is seen in the midline. There was severe cortical atrophy. The amnion (small black arrow) can be seen separating the diamniotic twins.
QUINN,
HUBBARD,
AND
ADZICK
motion with reduction in the quality of the scan. In addition, maternal obesity required a larger field of view that resulted in decreased fetal detail. However, the problems with fetal motion and maternal obesity did not prevent the identification of the anatomic malformation. DISCUSSION
We evaluated the usefulness of fetal MRI with ultrafast imaging sequences in the diagnosis and management of selected fetal anomalies referred to our center over the course of 1 year. Patients undergoing fetal MRI were surgery candidates undergoing a multidisciplinary evaluation for a congenital anomaly that was a potentially correctable lesion or a diagnostic dilemma. Although MRI using standard spin-echo sequences has been used in the past to determine fetal anatomy, fetal motion severely limited the quality and diagnostic utility of the scans. Maternal sedation or fetal paralysis were necessary to obtain useful images using these slower sequences? Our study used ultrafast MRI sequences that included fast gradient echo (less than 30-second acquisition time), half fourier single-shot turbo spin-echo sequences (Haste), and echo planar sequences (EPI) in which the anatomic sections are acquired sequentially, each in less than 1 second, thereby decreasing motion artifacts8 Although the diagnostic possibilities of fetal MRI are exciting, it is important to consider safety issues for the implementation of this new technique. All of the sequences used in this study are approved by the FDA and are considered safe. One long-term study evaluated 20 children who had undergone fetal MRI with EPI sequences between 21 weeks’ gestation and term. After 3 years follow-up there were no deleterious effects from fetal MR19 A survey of 1,915 pregnant MRI nurses and technicians showed no increase in the rate of fetal loss or anomalies compared with the general populationLO However, the study addressed the effect of working in a high static magnetic field and not the issues of the radiofrequency electromagnetic fields that occur in the bore of the magnet. These reviews are reassuring, but studies using high-strength MR in chick embryos have shown some teratologic effects. l1 Thus, we have limited our studies in the following fashion to reduce possible risks: (1) restriction of fetal MRI examinations to patients beyond 18 weeks’ gestation to minimize a possible teratologic effect; (2) although the Haste sequences have multiple inversion pulses that can theoretically increase the energy and heat deposited into the patient, the flip angles were decreased from the usual 180” to 120”, thereby significantly reducing the amount of energy depositions and (3) the studies were designed to obtain as much information with the fewest number of sequences possible. With recent advances in prenatal US diagnosis, CDH is
PRENATAL
MRI ENHANCES
FETAL
557
DIAGNOSIS
frequently diagnosed before birth. The mortality in CDH relates to the degree of pulmonary hypoplasia and associated pulmonary hypertension and has been estimated to be as high as 58%.12 Identifying possible predictors of decreased survival in CDH, including estimations of the residual lung area and determination of liver hemiation, is not always possible by ultrasound scan.4J3Identification of these features is highly dependent on the skill of the examiner. With MRI using ultrafast sequences there was excellent tissue contrast with greater tissue differentiation than that obtained with US. In particular, the fetal lungs were easily seen by MRI using Haste sequences. The fetal stomach, liver, and various mass lesions were also well visualized with this technique. Both the identity of the tissue and an estimation of the amount present in the chest could be assessed with MRI. Because the presence of herniated fetal liver within the fetal chest is a predictor of poor neonatal outcome and the position of the fetal liver may also affect selection of patients for fetal intervention for CDH using temporary tracheal occlusion, this information was helpful for counseling families. While some fetal lung masses regress spontaneously, some masses enlarge, compressing the residual lung causing pulmonary hypoplasia. These lesions can progress to compromise the vena cava and heart leading to fetal hydrops and death. I4 Although US is effective at assessing hydrops, estimating the degree of hypoplasia has been unsuccessful to date. We found MRI to be particularly effective at identifying the amount of residual fetal lung and differentiating it from chest masses. Two cases referred to us involved CDH mistaken for CCAM based on the presence of nonperistaltic bowel in the chest that may appear as a multicystic lesion similar to a CCAM on US. The MRI characteristics of gut are very different from that of lung and lung tumors, allowing their clear differentiation. Although we were able to differentiate between CCAM and BPS by MRI in this study, the distinction between the two can also be made by color flow Doppler US based on identification of a feeding systemic artery to the BPS.15 Although lung volumes were measured in all CDH and chest lesion cases, the experience is still too limited to draw conclusions regarding the extent of pulmonary hypoplasia. The ability to identify normal lung and evaluate lung volume may be crucial to assessthe degree of pulmonary hypoplasia in CDH, compressive lung masses, and giant omphalocele. As MRI technique is
refined and normal lung volume estimates determined, predictions of pulmonary hypoplasia may be possible. The large field of view provided by MRI contributed to the accurate diagnosis of very large fetal lesions in the neck and the abdomen. Compared with ultrasound examinations in which only a small part of the lesion may be present in the acoustic window, the whole lesion and its anatomic relations could be viewed on the MRI sections. The information about the impingement of the fetal airway and neck vessels by huge cervical masses was better delineated by MRI than by US and was crucial for planning the EXIT procedure, a technique for securing the airway in a fetus while placental perfusion is maintained.5,6 Conventional postnatal airway management may have precluded the survival of all of these patients for whom airway accessvia endotracheal tube placement or tracheostomy required up to 55 minutes of placental bypass. Cervical teratoma was differentiated from cystic hygroma by MRI. The anatomic information allowed appropriate family counseling for the likelihood of survival and extent of disability in these fetuses with masses that were often nearly the size of the fetus itself. MRI confers a clear advantage in the evaluation of the fetal brain. Normal gyral patterns, ventricular size, and patterns of neuronal migration have all been documented by MRI.16 The posterior fossa is best evaluated by MRI, with significant detail of the cerebellar vermis possible to confirm or exclude Dandy-Walker malformation, a difficult diagnosis to make -accurately by US.17 MRI is superior to ultrasonography for the purpose of excluding CNS anomalies in a fetus with a malformation that may be amenable to fetal therapy. Although US remains the standard for prenatal diagnosis and screening, the quality of the examination is dependent on the availability of high-quality ultrasound equipment and a skilled examiner. Prenatal MRI using ultrafast sequences is still in its infancy. However, in our prospective study we found MRI using ultrafast imaging sequences provides superior tissue contrast and a variety of imaging planes regardless of the fetal lie. Prenatal MRI is particularly helpful at improving the anatomic definition, clarifying the diagnosis, and identifying other associated abnormalities. Fetal MRI is a valuable adjunct to the evaluation of an abnormal fetus. ACKNOWLEDGMENT The authors acknowledge preparation of the manuscript.
the help of Lori
Howell,
RN, MS, in the
REFERENCES 1. D’Alton ME, DeChemey AH: Prenatal diagnosis. N Engl J Med 328:114-120, 1993 2. Garmel SH, D’ Alton ME: Diagnostic ultrasound in pregnancy: An overview. Semin Perinatol 18:117-132, 1994
3. Lewis DA, Reichart C. Bowerman R, et al: Prenatal ultrasound frequently fails to diagnose congenital diaphragmatic hernia. J Pediatr Surg 32:352-356, 1997 4. Metkus AP Filly RA, Stringer MD, et al: Sonographic predictors
QUINN,
of survival in fetal diaphragmatic hernia. J Pediatr Surg 31:148-152, 1996 5. Mychaliska GB, Bealer JF, Graf JL, et al: Operating on placental support: The Ex Utero Intrapartum Treatment (EXIT) procedure. J Pediatr Surg 32:227-231, 1997 6. Crombleholme TM, Hubbard AM, Howell LJ, et al: EXIT Procedure (Ex Utero Intrapartum Treatment) for giant fetal neck masses. Am J Obstet Gynecol 176S84, 1997 7. Weinreb JC, Lowe T, Cohen JM, et al: Human fetal anatomy. Radiology 157:715-720, 1985 8. Semelka RC, Kelekis NL, Thomason D, et al: HASTE MR imaging: Description of technique and preliminary results in the abdomen. J Magn Reson Imaging 6:698-699, 1996 9. Baker PN, Johnson DM, Harvey PR, et al: A three year follow-up of children imaged in utero with echo-planar magnetic resonance. Am J Obstet Gynecol 170:32-33, 1994 10. Kanal E, Gillen J, Evans JA, et al: Survey of reproductive health among female MR workers. Radiology 187:395-399, 1993
HUBBARD,
AND
ADZICK
11. Yip YP, Capriotti C, Talagala SL, et al: Effects of MR exposure at 1.5T on early embryonic development of the chick. J Magn Reson Imaging 4:742-748, 1994 12. Harrison MR, Adzick NS, Estes JM, et al: A prospective study of the outcome for fetuses with diaphragmatic hernia. JAMA 271:382-384, 1994 13. Bootstaylor BS, Filly RA, Harrison MR, et al: Prenatal sonographic predictors of liver hemiation in congenital diaphragmatic hernia. J Ultrasound Med 14:515-520,1995 14. Adzick NS, Harrison MR: Fetal surgical therapy. Lancet 343:897902, 1994 15. MacGillivray TE, Harrison MR, Goldstein RB, et al: Disappearing fetal lung lesions. J Pediatr Surg 28:1321-1325, 1993 16. Naidich TP, Grant IL, Altman N, et al: The developing cerebral surface. Neurosurg Clin North Am 4:201-240, 1994 17. Filly RA: Ultrasound evaluation of the fetal neural axis, in Callen PW (ed): Ultrasonography in Obstetrics and Gynecology, New York, NY, WB Saunders, 1994, pp 189-234