Lethal multiple pterygium syndrome, large cystic hygroma, and cleft palate: Rare and severe fetal presentations of RYR1- and NEB-related congenital myopathies.

Congenital myopathies are a genetically heterogeneous group of neuromuscular disorders that commonly present with congenital hypotonia and weakness but can also present broadly. The most severe presentation is neonatal with arthrogryposis and, rarely, fetal akinesia and pterygia, features also seen in lethal multiple pterygium syndrome (LMPS). We describe two fetuses with similar phenotype, including hydrops fetalis, large cystic hygromas, bilateral talipes, and fetal akinesia in the second trimester. Genetic diagnoses were made using exome sequencing. Both fetuses had a severe form of congenital myopathy. In the first fetus, we identified two novel compound heterozygous likely pathogenic variants consistent with autosomal recessive RYR1-related congenital myopathy (congenital myopathy 1B). In the second fetus, we identified two likely pathogenic variants, one of which is novel, likely in trans consistent with a diagnosis of autosomal recessive NEB-related congenital myopathy. Reaching a genetic diagnosis for these fetuses allowed the families to receive accurate genetic counseling for future pregnancies. These fetuses highlight the genetic and phenotypic heterogeneity of LMPS, and support a broad approach to genetic testing.

The Implementation of Preeclampsia Screening and Prevention (IMPRESS) Study.

BACKGROUND: Preeclampsia affects between 2% and 5% of pregnancies and is one of the leading causes of perinatal morbidity and mortality worldwide. Despite strong evidence that the combination of systematic preeclampsia screening based on the Fetal Medicine Foundation preeclampsia risk calculation algorithm with treatment of high-risk patients with low-dose aspirin reduces the incidence of preterm preeclampsia more than currently used risk-factor-based screening, real-world implementation studies have not yet been done in Canada. OBJECTIVE: This study aimed to assess the operational feasibility of implementing first-trimester screening and prevention of preterm preeclampsia (<37 weeks) alongside a publicly funded first-trimester combined screening program for aneuploidies. STUDY DESIGN: This was a prospective implementation study. Consecutive pregnant patients referred for first-trimester combined screening (11-13+6 weeks) were offered screening for preeclampsia based on the Fetal Medicine Foundation algorithm concomitantly with their aneuploidy screen. Consenting participants were screened using maternal risk factors, mean arterial pressure, uterine artery Doppler pulsatility index, pregnancy-associated plasma protein-A, and placental growth factor. Risk for preterm preeclampsia (<37 weeks) was calculated using the Fetal Medicine Foundation algorithm, and individuals with a risk score ≥1 per 100 were recommended to use aspirin (162 mg once daily at bedtime, <16-36 weeks). Implementation metrics assessed included: acceptability, operational impact, proportion of aspirin initiation, quality and safety measures, and screen performance. RESULTS: Between December 1, 2020 and April 23, 2021, 1124 patients consented to preeclampsia screening (98.3% uptake), and 92 (8.2%) screened positive. Appointments for patients receiving first-trimester combined screening aneuploidy and preeclampsia screening averaged 6 minutes longer than first-trimester combined screening alone, and adding uterine artery Doppler pulsatility index averaged 2 minutes. Of the 92 patients who screened as high-risk for preeclampsia, 72 (78.3%) were successfully contacted before 16 weeks' gestation. Of these, 62 (86.1%) initiated aspirin, and 10 (13.9%) did not. Performance audit identified a consistent negative bias with mean arterial pressure measurements (median multiple of the median <1 in 10%); other variables were satisfactory. There were 7 cases of preterm preeclampsia (0.69%): 5 and 2 in the high- and low-risk groups, respectively. Screening detected 5 of 7 (71.4 %) preterm preeclampsia cases, with improved performance after adjustment for aspirin treatment effect. CONCLUSION: This study confirms the operational feasibility of implementing an evidence-based preeclampsia screening and prevention program in a publicly funded Canadian setting. This will facilitate implementation into clinical service and the scaling up of this program at a regional and provincial level.

Human placental perfusion measured using dynamic contrast enhancement MRI.

OBJECTIVES: To evaluate the feasibility of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) and measure values of in vivo placental perfusion in women. METHODS: This study was part of the Placentimage trial (NCT01092949). Gadolinium-chelate (Gd) enhanced dynamic MRI was performed two days before termination of pregnancies at 16 to 34 weeks gestational age (GA). Quantitative analysis was performed using one-compartment intravascular modeling. DCE perfusion parameters were analyzed across GA and were compared in IUGR and AGA fetuses. RESULTS: 134 patients were enrolled. After quality control check, 62 DCE MRI were analyzed including 48 and 14 pregnancies with normal and abnormal karyotypes, respectively. Mean placental blood flow was 129±61 mL/min/100ml in cases with normal karyotypes. Fetuses affected by IUGR (n = 13) showed significantly lower total placental blood flow values than AGA fetuses (n = 35) (F total = 122±88 mL/min versus 259±34 mL/min, p = 0.002). DCE perfusion parameters showed a linear correlation with GA. CONCLUSIONS: Measuring placental perfusion in vivo is possible using DCE MRI. Although this study has many limitations it gives us the first DCE MRI values that provide a potential standard for future research into placental perfusion methods and suggests that placental functional parameters are altered in IUGR pregnancies.

Dynamic contrast enhanced magnetic resonance imaging: A review of its application in the assessment of placental function.

It is important to develop a better understanding of placental insufficiency given its role in common maternofetal complications such as preeclampsia and fetal growth restriction. Functional magnetic resonance imaging offers unprecedented techniques for exploring the placenta under both normal and pathological physiological conditions. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is an established and very robust method to investigate the microcirculatory parameters of an organ and more specifically its perfusion. It is currently a gold standard in the physiological and circulatory evaluation of an organ. Its application to the human placenta could enable to access many microcirculatory parameters relevant to the placental function such as organ blood flow, fractional blood volume, and permeability surface area, by the acquisition of serial images, before, during, and after administration of an intravenous contrast agent. Widely used in animal models with gadolinium-based contrast agents, its application to the human placenta could be possible if the safety of contrast agents in pregnancy is established or they are confirmed to not cross the placenta.

MRI based morphological examination of the placenta.

Ultrasound is widely used as the initial diagnostic imaging modality during pregnancy with both high spatial and temporal resolution. Although MRI in pregnancy has long focused on the fetus, its use in placental imaging has greatly increased over recent years. In addition to the possibilities of evaluating function, MRI with a wide field of view and high contrast resolution allows characterization of placental anatomy, particularly in situations that are difficult to specify with ultrasound, especially for suspected placenta accreta. MRI also appears to be a particularly useful examination for the anatomical evaluation of the placenta independent of maternal body habitus or fetal position. Indeed, surprisingly little attention is paid to the placenta in MRI when the indication for the examination is fetal. Thus, some aspects of the placenta seem to us to be important to be recognized by the radiologist and to be described on the MRI report. In this review, we will describe MRI sequences used for, and common features seen in, imaging of i) the normal placenta, ii) abnormal aspects of the placenta that should be identified on MRI performed for fetal reason, and iii) placental anomalies for which placental MRI may be indicated.

Ultrasound and Fetal MRI Complementary Contributions to Appropriate Counseling in Small Bowel Obstruction.

OBJECTIVE: Bowel obstructions beyond the duodenum represent a heterogeneous group of congenital anomalies with a highly variable prognosis, the main issue being postnatal short bowel syndrome (SBS). The objective of our study was to evaluate the contributions of fetal MRI in cases of bowel obstruction. MATERIALS AND METHODS: A retrospective analysis of all newborns, for whom both ante-natal ultrasound and fetal MRI were available, referred to our center for suspected bowel obstruction was performed. Examinations were reviewed blinded to the postnatal outcome. Key outcome measures included exact diagnosis and the existence of postoperative SBS. We evaluated the contribution of MRI in determining precise location and etiology of the bowel obstruction, dilatation of the proximal bowel loops, and assessment of the quality of the remaining distal bowel loops. RESULTS: Twenty-five newborns were included. There were 19 single obstructions and 6 complex forms (4 apple peel syndromes and 2 multiple atresias). MRI correctly identified the affected segment of the small bowel in 59.1% of the cases. MRI identified the mechanism of obstruction in 72% of cases. MRI reliably predicted an abnormal appearance of the bowel distal to the obstruction in 100% of the severe cases (3/3) and in 66.7% of complex forms (4/6). CONCLUSION: Our study suggests that fetal MRI, when done in addition to prenatal ultrasound, is contributory in the management of fetuses with suspected bowel obstruction. MRI may be particularly useful in determining the location and origin of the bowel obstruction and in assessing the quality of the bowel distal to the obstruction, which might assist in the prediction of SBS and more detailed prenatal counseling.

The use of fetal MRI for renal and urogenital tract anomalies.

Fetal anomalies are detected in approximately 2% of all fetuses and, among these, genitourinary tract abnormalities account for 30% to 50% of all structural anomalies present at birth. Although ultrasound remains the first line diagnostic modality, fetal MRI provides important additional structural and functional information, especially with the development of faster sequences and the use of functional sequences. The added value of MRI-based imaging is three-fold: (a) improvement of diagnostic accuracy by adequate morphological examination, (b) detection of additional anomalies, and (c) in addition, MRI has the potential to provide information regarding renal function. In this review, we describe the role of fetal MRI in the anatomical evaluation of renal and urogenital tract anomalies, and we also touch upon the contribution of functional MRI to the diagnostic workup of these conditions.

The use of image fusion in prenatal medicine.

Fusion imaging (FI), the simultaneous display of the same anatomical region using two imaging modalities, has been used in other areas of medicine for both diagnosis and guiding interventions. Examples include positron emission tomography-computed tomography (PET-CT) imaging in oncology and ultrasound-magnetic resonance imaging (US-MRI) fusion in biopsies of the prostate gland. The underlying principle is to take advantage of the complementary information in each modality to improve accuracy, be it diagnostic accuracy or targeting accuracy in biopsies. For example, PET-CT overlays the metabolic activity of lesions on the superb spatial and anatomical detail of CT. While the historical mainstay of fetal imaging has been ultrasound, advances in ultrafast MR imaging together with advances in fetal MRI over the past two decades, have resulted in the opportunity to explore fusion imaging in fetal medicine. We present an overview of the principles of US-MRI fusion imaging in prenatal medicine, report our local experience, and review the literature in this emerging area. We share our perspective on how FI can improve diagnostic confidence, be used as an educational tool, and potentially enhance guidance in certain fetal procedures.

Assessment of chronic renal allograft nephropathy using contrast-enhanced MRI: a pilot study.

OBJECTIVE: Renal allograft function monitoring has traditionally relied on functional markers such as creatinine level. Such markers are insensitive, and invasive ultrasound-guided protocol biopsies are used for allograft evaluation. This pilot study evaluates the association between renal perfusion measured noninvasively with contrast-enhanced MRI and the histologic severity of chronic allograft nephropathy. SUBJECTS AND METHODS: Chronic allograft nephropathy severity was estimated from protocol biopsy specimens using the chronic allograft damage index. We prospectively selected four patients considered to have severe chronic allograft nephropathy (chronic allograft damage index score > 4) and six patients considered to have stable allograft function (chronic allograft damage index score 4 than in the other patients (1.94 vs 2.43 mL/min/g, respectively; p = 0.03). The effect size for this difference was large (d = 1.7). The R(2) for the linear regression model was 0.53. CONCLUSION: We observed an association between contrast-enhanced MRI renal perfusion and chronic allograft nephropathy severity. Further studies are needed to confirm this preliminary finding and to evaluate the role of contrast-enhanced MRI renal perfusion as a screening test for allograft dysfunction and potential utility in patient management.

Dynamic half-Fourier single-shot turbo spin echo for assessment of deep venous thrombosis: initial observations.

OBJECTIVE: The objective of this study was to retrospectively analyze the value of dynamic half-Fourier single-shot turbo spin echo (HASTE) imaging in patients with suspected deep venous thrombosis (DVT). MATERIALS AND METHODS: Fifty-five veins in 24 patients were interrogated using a HASTE sequence with the patients relaxed and in various degrees of Valsalva. Veins were analyzed for changes in caliber (+CAL) and signal intensity (+SI) or in their absence (-CAL and -SI, respectively) and compared with the presence of thrombus on gadolinium-enhanced magnetic resonance imaging. RESULTS: There was no thrombus in veins with the +CAL, +SI pattern (n=40) (P<.01). Five of seven veins (71.4%) with the -CAL, -SI pattern had thrombus (P<.01). A qualitative change in CAL had a sensitivity of 100% and a specificity of 91% for the presence of thrombus. An increase of 1.5 mm in CAL had a sensitivity of 100% and a specificity of 93% for this diagnosis. CONCLUSION: Dynamic HASTE imaging offers a physiological method to evaluate veins for deep venous thrombosis.

Unenhanced MR angiography of the renal arteries with balanced steady-state free precession dixon method.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of a novel technique for fat-water separation to image the renal arteries without using a contrast agent. CONCLUSION: Five healthy volunteers were imaged on a 3-T clinical MR scanner using the balanced steady-state free precession (SSFP) Dixon method. We were able to image the proximal renal arteries with high conspicuity within a 3-minute overall scanning time. The balanced-SSFP Dixon method shows potential for unenhanced MR angiography of the proximal renal arteries.

3D non-contrast-enhanced MR angiography with balanced steady-state free precession Dixon method.

Balanced steady-state free precession (bSSFP) is capable of producing ample fat-water separation. In the case of the bSSFP Dixon method, the phase between fat and water can be manipulated by setting repetition time (TR) to an odd-half-multiple of the cycle time and adjusting the center frequency to acquire fat-water in in-phase and opposed-phase images. Adding an image collected when fat and water are in-phase to an image in which fat and water are opposed-phase produces a water-only image. Of the water signals, arterial blood has the highest T(2)/T(1) contrast, making the arterial signal appear brighter than both venous blood and muscle in the final image. In this study, the bSSFP Dixon method was used to collect coronal water-only three-dimensional (3D) volumes at multiple anatomical stations in the legs of five healthy volunteers. The image quality was quantified by region-of-interest (ROI) analysis of signal intensities between arterial blood, venous blood, muscle, and fat. The images were also assessed for diagnostic quality by a trained radiologist. The bSSFP Dixon method was successful in producing non-contrast-enhanced (NCE) images of the blood vessels in the lower limbs. The work presented here is a proof-of-concept for the use of the bSSFP Dixon method for 3D peripheral angiography.

Effect of frequent nocturnal hemodialysis vs conventional hemodialysis on left ventricular mass and quality of life: a randomized controlled trial.

CONTEXT: Morbidity and mortality rates in hemodialysis patients remain excessive. Alterations in the delivery of dialysis may lead to improved patient outcomes. OBJECTIVE: To compare the effects of frequent nocturnal hemodialysis vs conventional hemodialysis on change in left ventricular mass and health-related quality of life over 6 months. DESIGN, SETTING, AND PARTICIPANTS: A 2-group, parallel, randomized controlled trial conducted at 2 Canadian university centers between August 2004 and December 2006. A total of 52 patients undergoing hemodialysis were recruited. INTERVENTION: Participants were randomly assigned in a 1:1 ratio to receive nocturnal hemodialysis 6 times weekly or conventional hemodialysis 3 times weekly. MAIN OUTCOME MEASURES: The primary outcome was change in left ventricular mass, as measured by cardiovascular magnetic resonance imaging. The secondary outcomes were patient-reported quality of life, blood pressure, mineral metabolism, and use of medications. RESULTS: Frequent nocturnal hemodialysis significantly improved the primary outcome (mean left ventricular mass difference between groups, 15.3 g, 95% confidence interval [CI], 1.0 to 29.6 g; P = .04). Frequent nocturnal hemodialysis did not significantly improve quality of life (difference of change in EuroQol 5-D index from baseline, 0.05; 95% CI, -0.07 to 0.17; P = .43). However, frequent nocturnal hemodialysis was associated with clinically and statistically significant improvements in selected kidney-specific domains of quality of life (P = .01 for effects of kidney disease and P = .02 for burden of kidney disease). Frequent nocturnal hemodialysis was also associated with improvements in systolic blood pressure (P = .01 after adjustment) and mineral metabolism, including a reduction in or discontinuation of antihypertensive medications (16/26 patients in the nocturnal hemodialysis group vs 3/25 patients in the conventional hemodialysis group; P < .001) and oral phosphate binders (19/26 patients in the nocturnal hemodialysis group vs 3/25 patients in the conventional dialysis group; P < .001). No benefit in anemia management was seen with nocturnal hemodialysis. CONCLUSION: This preliminary study revealed that, compared with conventional hemodialysis (3 times weekly), frequent nocturnal hemodialysis improved left ventricular mass, reduced the need for blood pressure medications, improved some measures of mineral metabolism, and improved selected measures of quality of life. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN25858715.

Magnetization evolution in balanced steady-state free precession with continuously moving table.

Diagnostic imaging of systemic disorders, such as peripheral vascular diseases, requires a field-of-view (FOV) larger than the local FOV available on clinical MR scanners. The continuously moving table (CMT) method acquires large FOV images in a single acquisition. Balanced steady-state free precession (bSSFP) is an attractive candidate for the CMT method due to its short repetition time and high signal-to-noise ratio. However, introducing table motion during data acquisition perturbs the magnetization evolution towards steady state. In this paper, a computer model was developed to simulate the bSSFP magnetization evolution in the presence of table motion. From these simulations, predictions were made about the maximum table velocities that would allow the magnetizations of specific tissues to evolve to the theoretical steady-state values. These predicted maximum table velocities were then successfully verified in vivo with bSSFP CMT acquisitions. For an imaging FOV

MR-guided ablation of hepatocellular carcinoma aided by gadoxetic acid.

Local recurrences are problematic following radiofrequency ablation (RFA) of hepatocellular carcinoma. Intraoperative magnetic resonance imaging (iMRI) is a potentially useful tool for the assessment of the extent of the thermal injury produced by RFA. The use of gadoxetic acid disodium, a hepatocyte-specific contrast agent with prolonged retention, is described as a method of improved assessment of the ablative margins relative to the tumor margins.

Time-efficient breath-hold abdominal MRI at 3.0 T.

OBJECTIVE: The purpose of this study was to increase the allowed number of acquired slices per unit time (i.e., time efficiency) for high-power deposition breath-hold abdominal acquisitions at 3.0 T. MATERIALS AND METHODS: Abdominal MRI protocols include various T1-weighted, T2-weighted, and contrast-enhanced acquisitions that require extended spatial coverage and resolution. Ideally, each acquisition is completed within one breath-hold. At 3.0 T, power deposition (i.e., specific absorption rate [SAR]) concerns can limit achieving these conflicting needs because conventional sequences are based on 6-minute time-average SAR requirements. We optimized abdominal-specific sequences based on an approved short-term 10-second time-average SAR criterion and added a delay time after breath-holding to fulfill the long-term 6-minute time-average power deposition regulation. RESULTS: Using our strategy, image acquisition time efficiency at 3.0 T was increased approximately twofold compared with conventional abdominal breath-hold pulse sequences for 2D dual-echo gradient-recalled echo, single-shot fast spin-echo, and 3D steady-state free precession sequences. Volunteers experienced a slight sensation of warmth for the single-shot fast spin-echo implementation, the most SAR-intensive sequence. CONCLUSION: Our optimization strategy is not vendor-specific, is easily implemented for all conventional scanners (provided one can access and modify the pulse sequences directly, or the vendors can make the necessary changes), yields a higher slice-per-unit-time imaging efficiency, and still satisfies all the regulatory power deposition requirements.

Complex hepatic surgery aided by a 1.5-tesla moveable magnetic resonance imaging system.

BACKGROUND: Resection represents the best treatment for potentially curable liver tumors; radiofrequency ablation (RFA) is an alternative. The curative potential of RFA may be hampered because the extent of burn is difficult to estimate by ultrasound. We postulated that intraoperative MRI (iMRI) would enable a more accurate assessment of ablation completeness. METHODS: We performed open hepatic surgery in an operating room equipped with a unique, retractable 1.5-T magnet. Patients were selected because it was anticipated that RFA (with or instead of resection) was likelihood and that iMRI might be helpful in making intraoperative decisions. After baseline MRI, lesions were further assessed by ultrasound at the time of open surgery. Lesions were resected and/or ablated, and further imaging confirmed the margins of the procedure. RESULTS: Nine patients underwent the procedure: 1 with metastatic carcinoid, 4 with hepatocellular carcinoma, and 4 with colorectal liver metastases. In 4 patients, iMRI had an effect on decision-making. In 5 individuals, there were nonlocal recurrences, and 1 patient who was never disease-free had a local recurrence. COMMENTS: Intraoperative MRI could potentially impact operative decision-making when ablating extensive disease. Its ability to prevent local recurrences must be determined. Moreover, the role of this technology in the overall treatment armamentarium must be defined.

MR imaging of the prostate at 3 Tesla: comparison of an external phased-array coil to imaging with an endorectal coil at 1.5 Tesla.

RATIONALE AND OBJECTIVES: To qualitatively compare the image quality of torso phased-array 3-Tesla (3T) imaging of the prostate with that of endorectal 1.5-Tesla imaging. MATERIALS AND METHODS: Twenty cases of torso phased-array prostate imaging performed at 3-Tesla with FSE T2 weighted images were evaluated by two readers independently for visualization of the posterior border (PB), seminal vesicles (SV), neurovascular bundles (NVB), and image quality rating (IQR). Studies were performed at large fields of view(FOV) (25 cm) (14 cases) (3TL) and smaller FOV (14 cm) (19 cases) (3TS). A comparison was made to 20 consecutive cases of 1.5-T endorectal evaluation performed during the same time period.Results. 3TL produced a significantly better image quality compared with the small FOV for PB (P = .0001), SV (P =.0001), and IQR (P = .0001). There was a marginally significant difference within the NVB category (P = .0535). 3TL produced an image of similar quality to image quality at 1.5 T for PB (P = .3893), SV (P = .8680), NB (P = .2684), and IQR (P = .8599). CONCLUSION: Prostate image quality at 3T with a torso phased-array coil can be comparable with that of endorectal 1.5-T imaging. These findings suggest that additional options are now available for magnetic resonance imaging of the prostate gland.

Visualization and quantification of renal R2* changes during water diuresis.

PURPOSE: To refine and evaluate methods for analysis of renal blood oxygenation level dependent (BOLD) MRI data. MATERIALS AND METHODS: Color R2* maps and regions-of-interest (ROIs) on the borderline between cortex and medulla were applied to renal BOLD MRI data of a group of 13 young female subjects. RESULTS: The distribution of R2* within the kidneys was heterogeneous and the response of human kidneys to water diuresis was patchy. R2* values at the cortico-medullary border region have a smaller variation than in wider cortical or medullary regions and are sensitive to physiological changes produced by water diuresis. CONCLUSION: These methods provide improved visualization of the regional distribution of R2* and its variations and more precise quantification of the changes in renal R2* produced by water diuresis.