RASopathies for Radiologists.

RASopathies are a heterogeneous group of genetic syndromes caused by germline mutations in a group of genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) signaling pathway. RASopathies include neurofibromatosis type 1, Legius syndrome, Noonan syndrome, Costello syndrome, cardiofaciocutaneous syndrome, central conducting lymphatic anomaly, and capillary malformation-arteriovenous malformation syndrome. These disorders are grouped together as RASopathies based on our current understanding of the Ras/MAPK pathway. Abnormal activation of the Ras/MAPK pathway plays a major role in development of RASopathies. The individual disorders of RASopathies are rare, but collectively they are the most common genetic condition (one in 1000 newborns). Activation or dysregulation of the common Ras/MAPK pathway gives rise to overlapping clinical features of RASopathies, involving the cardiovascular, lymphatic, musculoskeletal, cutaneous, and central nervous systems. At the same time, there is much phenotypic variability in this group of disorders. Benign and malignant tumors are associated with certain disorders. Recently, many institutions have established multidisciplinary RASopathy clinics to address unique therapeutic challenges for patients with RASopathies. Medications developed for Ras/MAPK pathway-related cancer treatment may also control the clinical symptoms due to an abnormal Ras/MAPK pathway in RASopathies. Therefore, radiologists need to be aware of the concept of RASopathies to participate in multidisciplinary care. As with the clinical manifestations, imaging features of RASopathies are overlapping and at the same time diverse. As an introduction to the concept of RASopathies, the authors present major representative RASopathies, with emphasis on their imaging similarities and differences. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Divergent growth of the transient brain compartments in fetuses with nonsyndromic isolated clefts involving the primary and secondary palate.

Cleft lip/palate is a common orofacial malformation that often leads to speech/language difficulties as well as developmental delays in affected children, despite surgical repair. Our understanding of brain development in these children is limited. This study aimed to analyze prenatal brain development in fetuses with cleft lip/palate and controls. We examined in utero MRIs of 30 controls and 42 cleft lip/palate fetal cases and measured regional brain volumes. Cleft lip/palate was categorized into groups A (cleft lip or alveolus) and B (any combination of clefts involving the primary and secondary palates). Using a repeated-measures regression model with relative brain hemisphere volumes (%), and after adjusting for multiple comparisons, we did not identify significant differences in regional brain growth between group A and controls. Group B clefts had significantly slower weekly cerebellar growth compared with controls. We also observed divergent brain growth in transient brain structures (cortical plate, subplate, ganglionic eminence) within group B clefts, depending on severity (unilateral or bilateral) and defect location (hemisphere ipsilateral or contralateral to the defect). Further research is needed to explore the association between regional fetal brain growth and cleft lip/palate severity, with the potential to inform early neurodevelopmental biomarkers and personalized diagnostics.

Exploring patient experiences of participating in digital cardiac rehabilitation: A qualitative study.

OBJECTIVE: Digital cardiac rehabilitation (CR) has emerged as a promising alternative to in-person CR. Understanding patients' experiences and perceptions can provide valuable insights into what makes these programmes successful and identify opportunities for improvement. This study aimed to explore patients' experiences of digital CR and to understand the factors that make these programmes successful. DESIGN: A qualitative approach was taken. METHODS: From March to August 2022, we conducted semi-structured interviews with patients who were referred to one of two digital CR programmes offered on the island of Ireland. Interviews were audio-recorded, transcribed verbatim and analysed using reflexive thematic analysis. A public and patient involvement panel guided the recruitment strategy and assisted with data analysis. RESULTS: Eleven patients, predominantly male (82%) and with a mean age of 64 (range 50-75), participated in the study. Five themes were developed: (1) Empowered patients; (2) Controlling the recovery; (3) At home but not alone; (4) The world at your (digital) doorstep and; (5) Challenges of interacting online. Participants reported that digital CR equipped them with the necessary tools and support to modify their lifestyle and effectively manage their recovery. However, the opportunities for social interaction were limited and communicating online was not always straightforward. CONCLUSIONS: Participants reported that digital CR guided them towards recovery and improved their sense of empowerment and control. However, the limited opportunities for social interaction may represent a challenge for patients seeking social support.

Atypical fetal brain development in fetuses with non-syndromic isolated musculoskeletal birth defects (niMSBDs).

Non-syndromic, isolated musculoskeletal birth defects (niMSBDs) are among the leading causes of pediatric hospitalization. However, little is known about brain development in niMSBDs. Our study aimed to characterize prenatal brain development in fetuses with niMSBDs and identify altered brain regions compared to controls. We retrospectively analyzed in vivo structural T2-weighted MRIs of 99 fetuses (48 controls and 51 niMSBDs cases). For each group (19-31 and >31 gestational weeks (GW)), we conducted repeated-measures regression analysis with relative regional volume (% brain hemisphere) as a dependent variable (adjusted for age, side, and interactions). Between 19 and 31GW, fetuses with niMSBDs had a significantly (P < 0.001) smaller relative volume of the intermediate zone (-22.9 ± 3.2%) and cerebellum (-16.1 ± 3.5%,) and a larger relative volume of proliferative zones (38.3 ± 7.2%), the ganglionic eminence (34.8 ± 7.3%), and the ventricles (35.8 ± 8.0%). Between 32 and 37 GW, compared to the controls, niMSBDs showed significantly smaller volumes of central regions (-9.1 ± 2.1%) and larger volumes of the cortical plate. Our results suggest there is altered brain development in fetuses with niMSBDs compared to controls (13.1 ± 4.2%). Further basic and translational neuroscience research is needed to better visualize these differences and to characterize the altered development in fetuses with specific niMSBDs.

Cross-Sectional Observational Study of Typical in utero Fetal Movements Using Machine Learning.

Early variations of fetal movements are the hallmark of a healthy developing central nervous system. However, there are no automatic methods to quantify the complex 3D motion of the developing fetus in utero. The aim of this prospective study was to use machine learning (ML) on in utero MRI to perform quantitative kinematic analysis of fetal limb movement, assessing the impact of maternal, placental, and fetal factors. In this cross-sectional, observational study, we used 76 sets of fetal (24-40 gestational weeks [GW]) blood oxygenation level-dependent (BOLD) MRI scans of 52 women (18-45 years old) during typical pregnancies. Pregnant women were scanned for 5-10 min while breathing room air (21% O2) and for 5-10 min while breathing 100% FiO2 in supine and/or lateral position. BOLD acquisition time was 20 min in total with effective temporal resolution approximately 3 s. To quantify upper and lower limb kinematics, we used a 3D convolutional neural network previously trained to track fetal key points (wrists, elbows, shoulders, ankles, knees, hips) on similar BOLD time series. Tracking was visually assessed, errors were manually corrected, and the absolute movement time (AMT) for each joint was calculated. To identify variables that had a significant association with AMT, we constructed a mixed-model ANOVA with interaction terms. Fetuses showed significantly longer duration of limb movements during maternal hyperoxia. We also found a significant centrifugal increase of AMT across limbs and significantly longer AMT of upper extremities <31 GW and longer AMT of lower extremities >35 GW. In conclusion, using ML we successfully quantified complex 3D fetal limb motion in utero and across gestation, showing maternal factors (hyperoxia) and fetal factors (gestational age, joint) that impact movement. Quantification of fetal motion on MRI is a potential new biomarker of fetal health and neuromuscular development.

Grains of Sand to Clinical Pearls: Realizing the Potential of Wearable Data.

Despite the rapid growth of wearables as a consumer technology sector and a growing evidence base supporting their use, they have been slow to be adopted by the health system into clinical care. As regulatory, reimbursement, and technical barriers recede, a persistent challenge remains how to make wearable data actionable for clinicians-transforming disconnected grains of wearable data into meaningful clinical "pearls". In order to bridge this adoption gap, wearable data must become visible, interpretable, and actionable for the clinician. We showcase emerging trends and best practices that illustrate these 3 pillars, and offer some recommendations on how the ecosystem can move forward.

Abnormal development of transient fetal zones in mild isolated fetal ventriculomegaly.

Mild isolated fetal ventriculomegaly (iFVM) is the most common abnormality of the fetal central nervous system. It is characterized by enlargement of one or both of the lateral ventricles (defined as ventricular width greater than 10 mm, but less than 12 mm). Despite its high prevalence, the pathophysiology of iFVM during fetal brain development and the neurobiological substrate beyond ventricular enlargement remain unexplored. In this work, we aimed to establish the relationships between the structural development of transient fetal brain zones/compartments and increased cerebrospinal fluid volume. For this purpose, we used in vivo structural T2-weighted magnetic resonance imaging of 89 fetuses (48 controls and 41 cases with iFVM). Our results indicate abnormal development of transient zones/compartments belonging to both hemispheres (i.e. on the side with and also on the contralateral side without a dilated ventricle) in fetuses with iFVM. Specifically, compared to controls, we observed enlargement of proliferative zones and overgrowth of the cortical plate in iFVM with associated reduction of volumes of central structures, subplate, and fetal white matter. These results indicate that enlarged lateral ventricles might be linked to the development of transient fetal zones and that global brain development should be taken into consideration when evaluating iFVM.

A threshold volume of 10 ml is suggested for detecting articular cartilage defects in equine carpal joints using CT arthrography: Ex vivo pilot study.

Computed tomographic arthrography (CTA) has been described as a method for detecting articular cartilage defects in equine carpal joints; however, published studies on the effects of contrast volume for lesion detection are currently lacking. The purpose of this prospective, experimental, pilot study was to determine a threshold volume of iodinated contrast for CTA of the antebrachiocarpal (ABC) and middle carpal (MC) joints for detection of articular cartilage surface defects. Articular cartilage defects were iatrogenically created in the surfaces of the ABC and MC joints of 20 equine cadaver limbs using arthroscopy. Unaltered articular surfaces within some joints acted as controls. Joints were imaged precontrast using multidetector CT. The ABC and MC joints were injected with a 150 mg iodine/ml nonionic contrast medium, in 5 ml increments from 5 to 50 ml per joint with CT performed subsequent to each increment. Cartilage defects were measured grossly using a caliper. Detection (qualitative) and measurement (quantitative) of the defects were independently performed by two board-certified radiologists using medical imaging software. At each volume of contrast, the interrater reliability for gross examination and the two observers in the detection of a defect was calculated (Gwet's AC1). Logistic mixed-effects models of selected volumes, 0, 5, 10, 15, and 50 ml, demonstrated that at 10 ml contrast and above, no statistically significant difference between either observer and gross examination for defect detection was identified for either joint. Findings supported using a dose of 10 ml for 150 mg iodine/ml concentration contrast media when performing CTA of equine carpal joints.

Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment.

BACKGROUND: Most people who begin statins abandon them, most commonly because of side effects. OBJECTIVES: The purpose of this study was to assess daily symptom scores on statin, placebo, and no treatment in participants who had abandoned statins. METHODS: Participants received 12 1-month medication bottles, 4 containing atorvastatin 20 mg, 4 placebo, and 4 empty. We measured daily symptom intensity for each using an app (scale 1-100). We also measured the "nocebo" ratio: the ratio of symptoms induced by taking statin that was also induced by taking placebo. RESULTS: A total of 60 participants were randomized and 49 completed the 12-month protocol. Mean symptom score was 8.0 (95% CI: 4.7-11.3) in no-tablet months. It was higher in statin months (16.3; 95% CI: 13.0-19.6; P < 0.001), but also in placebo months (15.4; 95% CI: 12.1-18.7; P < 0.001), with no difference between the 2 (P = 0.388). The corresponding nocebo ratio was 0.90. In the individual-patient daily data, neither symptom intensity on starting (OR: 1.02; 95% CI: 0.98-1.06; P = 0.28) nor extent of symptom relief on stopping (OR: 1.01; 95% CI: 0.98-1.05; P = 0.48) distinguished between statin and placebo. Stopping was no more frequent for statin than placebo (P = 0.173), and subsequent symptom relief was similar between statin and placebo. At 6 months after the trial, 30 of 60 (50%) participants were back taking statins. CONCLUSIONS: The majority of symptoms caused by statin tablets were nocebo. Clinicians should not interpret symptom intensity or timing of symptom onset or offset (on starting or stopping statin tablets) as indicating pharmacological causation, because the pattern is identical for placebo. (Self-Assessment Method for Statin Side-effects Or Nocebo [SAMSON]; NCT02668016).

The pediatric stomach - congenital abnormalities.

Diagnostic imaging of the pediatric stomach often provides a challenge for practicing radiologists. Radiologists should be aware of relatively unusual congenital pathology, especially when imaging very young children with gastrointestinal symptoms. We review congenital pathology of the pediatric stomach.

Temporal Pattern of Radiographic Findings of Costochondral Junction Rib Fractures on Serial Skeletal Surveys in Suspected Infant Abuse.

BACKGROUND. Costochondral junction (CCJ) rib fractures pose a challenge in the radiographic detection and dating of infant abuse. OBJECTIVE. The purpose of this article was to assess the temporal pattern of radio-graphic findings of CCJ fractures on a serial skeletal survey (SS). METHODS. Reports of SSs performed for suspected infant abuse were reviewed to identify those reporting a CCJ fracture. Study inclusion required undergoing initial and approximately 2-week follow-up SSs that included anteroposterior and bilateral oblique radiographs of the reported CCJ rib fracture. Two pediatric radiologists retrospectively classified fractures in terms of the primary injury pattern (bucket-handle: visible crescentic fracture line; corner: visible triangular fracture line; other) and secondary healing pattern (growth disturbance; sclerosis; subperiosteal new bone formation [SPNBF]). Discrepant readings were resolved by consensus. RESULTS. The final cohort included 26 infants with 81 CCJ fractures. On initial SS, 59% (48/81) of fractures showed a primary pattern, most commonly a bucket-handle pattern (46%; 37/81); 6% (5/81) showed a primary pattern on follow-up SS (p < .001). On initial SS, the prevalence of a secondary pattern was 89% (72/81), most commonly a growth disturbance (85%; 69/81), followed by sclerosis (57%; 46/81); 80% (65/81) showed a secondary pattern on follow-up SS (p = .12). Overall prevalence of SPNBF was 28% (23/81). Addition of bilateral oblique views on initial SS resulted in a significant increase relative to the anteroposterior views alone in the detection of primary and secondary patterns by 15% (p = .04) and 30% (p < .001), respectively. CONCLUSION. A bucket-handle appearance is the most common primary pattern of fracture. The significantly lower prevalence of a primary pattern on follow-up vs initial SSs suggests that the CCJ fracture line is usually visible for only approximately 2 weeks. A growth disturbance of the rib end is the most common secondary pattern, followed by bony sclerosis, consistent with a healing injury. SPNBF is uncommon. Most CCJ fractures are in a healing phase at initial diagnosis. The signs of repair commonly remain visible on 2-week follow-up. The increased diagnostic yield of oblique views provides support to the inclusion of these projections in routine SS protocols. CLINICAL IMPACT. The findings will help radiologists improve the diagnosis and dating of CCJ rib fractures.

Evaluation of a Community-Based Cardiovascular Prevention Program in Patients With Type 2 Diabetes.

PURPOSE: An outcomes' evaluation of a community-based cardiovascular disease (CVD) prevention program in persons with newly diagnosed type 2 diabetes. DESIGN: A prospective, observational study. SETTING: A community-setting in Ireland. PARTICIPANTS: Persons with newly diagnosed type 2 diabetes, aged 40 years or older, and 2 or more cardiovascular risk factors. INTERVENTION: A 16-week community-based, cardiovascular prevention program, with health promotion seminars, group exercise, and individual consultations, delivered by a multidisciplinary team. MEASURES: Medical, lifestyle, and well-being measures. ANALYSIS: Changes in categorical and continuous variables were analyzed using the paired exact test and the t test/Wilcoxin matched-pairs test, respectively. RESULTS: In total, 218 persons (134 men) participated, mean age was 59.8 (10.2) years. Completion rate was 75.2% (n = 164). The proportion achieving target glycosylated hemoglobin (HbA1c) increased from 53% at baseline to 75% (P < .001) at end of program. Systolic and diastolic blood pressures reduced by 8.8 mm Hg (95% CI: -11.2 to -6.4, P < .001) and 5.2 mm Hg (95% CI: -6.9 to -3.5, P < .001), respectively. Mean low-density lipoprotein cholesterol reduced from 2.45 to 2.05 mmol/L (P < .001). Significantly higher proportions met recommended targets in diet (6.9% vs 43.4%, P < .001) and physical activity (9.2% vs 56.6%, P < .001). Psychosocial measures significantly improved at end of program. The majority of improvements were sustained at 1 year. CONCLUSION: Participation in this CVD prevention program was associated with significant improvements in glycemia and CVD risk factors in newly diagnosed patients with type 2 diabetes.

Imaging features of pathologically proven pediatric splenic masses.

Splenic masses present a diagnostic challenge to radiologists and clinicians alike, with a relative paucity of data correlating radiologic findings to pathological diagnosis in the pediatric population. To illustrate splenic mass imaging findings and approximate lesion prevalence, we retrospectively reviewed all splenectomies and splenic biopsies for splenic masses at a single academic pediatric hospital over a 10-year period in patients 18 years and younger. A total of 31 splenic masses were analyzed. Lesion prevalence, pathology and imaging features associated with sampled splenic masses are described. The lesions encountered include benign splenic cysts (9), vascular anomalies (7), hamartoma (3), leukemia/lymphoma (3), granulomata (3) and metastasis (2). We also identified single cases of angiosarcoma, splenic cord capillary hemangioma, congestive hemorrhage, and benign smooth muscle neoplasm.

The pediatric stomach - masses and mass-like pathology.

Diagnostic imaging of pediatric gastric masses often provides a challenge for the practicing radiologist. Radiologists should be aware of this relatively unusual pathology, particularly in cross-sectional imaging findings. We will review pediatric gastric masses and mass-like lesions, focusing on neoplastic and inflammatory etiologies.

Standing CT of the equine head: Reducing radiation dose maintains image quality.

Multiple published studies involving computed tomographic (CT) examinations of the equine head utilise a wide range of mAs parameters for image acquisition. This prospective, experimental study assessed the effects of lowering mAs during CT image acquisition on image quality and scatter radiation on 10 cadaver equine heads. Each head was scanned three times at 300, 225, and 150 mAs, with all other scanning parameters remaining constant between series. An anthropomorphic phantom was positioned adjacent to each equine head during image acquisition, mimicking a human bystander, with an ionization chamber attached to the phantom at eye level. Each series was reconstructed using filtered back projection, using medium (H30) and high (H80) frequency reconstruction algorithms. Quantitative image quality assessment was performed by calculating signal to noise ratio (SNR) and contrast to noise ratio (CNR). Two qualitative image quality assessments were performed independently by three blinded board certified veterinary radiologists with a 4 week interval, using a visual grade analysis model adapted from peer reviewed medical literature. Ionization chamber measurements, calculated volume CT dose index (CTDIvol), and dose-length product (DLP) were recorded. Halving radiation dose during image acquisition from 300 to 150mAs resulted in comparable image quality between series. There was a statistically significant and linear relationship between mAs and scatter radiation to the bystander; halving mAs during image acquisition resulted in halving of scatter radiation. Results of this cadaveric study support the use of lower mAs settings during standing CT examinations of the equine head.

Fetal Echoplanar Imaging: Promises and Challenges.

Fetal magnetic resonance imaging (MRI) has been gaining increasing interest in both clinical radiology and research. Echoplanar imaging (EPI) offers a unique potential, as it can be used to acquire images very fast. It can be used to freeze motion, or to get multiple images with various contrast mechanisms that allow studying the microstructure and function of the fetal brain and body organs. In this article, we discuss the current clinical and research applications of fetal EPI. This includes T2*-weighted imaging to better identify blood products and vessels, using diffusion-weighted MRI to investigate connections of the developing brain and using functional MRI (fMRI) to identify the functional networks of the developing brain. EPI can also be used as an alternative structural sequence when banding or standing wave artifacts adversely affect the mainstream sequences used routinely in structural fetal MRI. We also discuss the challenges with EPI acquisitions, and potential solutions. As EPI acquisitions are inherently sensitive to susceptibility artifacts, geometric distortions limit the use of high-resolution EPI acquisitions. Also, interslice motion and transmit and receive field inhomogeneities may create significant artifacts in fetal EPI. We conclude by discussing promising research directions to overcome these challenges to improve the use of EPI in clinical and research applications.

Assessing the Effect of Packing the Sulcus on Image Quality in Equine Digital Radiography.

The requirement to pack the sulcus of the equine foot as an aid to diagnostic interpretation before acquisition of dorsoproximal-palmarodistal oblique projections is debatable. The purpose of this study was to investigate the benefit of packing the sulcus in the assessment of normal anatomy. 23 cadaver limbs were radiographed in a podoblock (https://www.podoblock.com/products-page/podoblock/podoblock/) A non-packed image (NP) and a packed image (P) of the same foot were acquired. The image quality of P was graded against the reference NP by five observers, where -1=P was superior, 0=no difference between P and NP, and +1=NP was superior. Four anatomical criteria were used: the distal solar margin of the distal phalanx (DP), the vascular channels of DP, the palmar aspect of the distal interphalangeal joint and the articulation of the navicular bone with DP. A total Visual Grading Analysis Score of 0.28 indicates a preference for NP images. Packing was of benefit in only 10.8 per cent of cases. While judicious high-quality packing may be of benefit in a minority of cases, the routine packing of the sulcus in equine radiography was not found to be of benefit in the assessment of anatomical features in this study.

Subperiosteal new bone formation with the distal tibial classic metaphyseal lesion: prevalence on radiographic skeletal surveys.

BACKGROUND: The classic metaphyseal lesion (CML) is a strong indicator of infant abuse, and the distal tibia is one of the most common sites for this injury. OBJECTIVE: To determine the prevalence of subperiosteal new bone formation accompanying the distal tibial CMLs identified on infant skeletal surveys. MATERIALS AND METHODS: Skeletal surveys performed for suspected infant abuse (2005-2017) were reviewed. Inclusion criteria were 1) anteroposterior (AP) and lateral radiographs of a distal tibial CML from the initial survey, 2) AP radiograph from the 2-week follow-up survey, 3) additional fractures, 4) child protection team consults and 5) mandated report filing for suspected abuse. We identified 22 distal tibial CMLs from 16 infants. Radiographs of these lesions were shown on the picture archiving and communication system to two blinded pediatric radiologists. Readers indicated the presence/absence of subperiosteal new bone formation on individual and combinations of images. RESULTS: Inter-reader agreements were fair (kappa=0.47). The prevalence of subperiosteal new bone formation on initial AP radiograph was 34%. Significant increases in the prevalence were found with the addition of follow-up AP radiograph (57%; P<0.001), initial lateral radiograph (57%; P=0.002) and follow-up AP plus initial lateral radiographs (71%; P<0.001). Statistically significant increases in prevalence were also noted when the third view was added to the other two views (increase of 14%; P=0.024). CONCLUSION: Even when skeletal surveys include initial AP, lateral and follow-up AP radiographs of the tibia, nearly one-third of distal tibial CMLs will fail to demonstrate subperiosteal new bone formation.

Metadata Correction: Direct Adherence Measurement Using an Ingestible Sensor Compared With Self-Reporting in High-Risk Cardiovascular Disease Patients Who Knew They Were Being Measured: Prospective Intervention.

[This corrects the article DOI: 10.2196/mhealth.6998.].