Imaging of pediatric hematopoietic stem cell transplant recipients: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Imaging in hematopoietic stem cell transplantation patients is not targeted at evaluating the transplant per se. Rather, imaging is largely confined to evaluating peri-procedural and post-procedural complications. Alternatively, imaging may be performed to establish a baseline study for comparison should the patient develop certain post-procedural complications. This article looks to describe the various imaging modalities available with recommendations for which imaging study should be performed in specific complications. We also provide select imaging protocols for different indications and modalities for the purpose of establishing a set minimal standard for imaging in these complex patients.

Competency Standard Derivation for Point-of-Care Ultrasound Image Interpretation for Emergency Physicians.

STUDY OBJECTIVE: Because number-based standards are increasingly controversial, the objective of this study was to derive a performance-based competency standard for the image interpretation task of point-of-care ultrasound (POCUS). METHODS: This was a prospective study. Operating on a clinically-relevant sample of POCUS images, we adapted the Ebel standard-setting method to derive a performance benchmark in 4 diverse pediatric POCUS applications: soft tissue, lung, cardiac and focused assessment with sonography in trauma (FAST). In Phase I (difficulty calibration), cases were categorized into interpretation difficulty terciles (easy, intermediate, hard) using emergency physician-derived data. In Phase II (significance), a 4-person expert panel categorized cases as low, medium, or high clinical significance. In Phase III (standard setting), a 3x3 matrix was created, categorizing cases by difficulty and significance, and a 6-member panel determined acceptable accuracy for each of the 9 cells. An overall competency standard was derived from the weighted sum. RESULTS: We obtained data from 379 emergency physicians resulting in 67,093 interpretations and a median of 184 (interquartile range, 154, 190) interpretations per case. There were 78 (19.5%) easy, 272 (68.0%) medium, and 50 (12.5%) hard-to-interpret cases, and 237 (59.3%) low, 65 (16.3%) medium, and 98 (24.5%) cases of high clinical significance across the 4 POCUS applications. The panel determined an overall performance-based competency score of 85.0% for lung, 89.5% for cardiac, 90.5% for soft tissue, and 92.7% for FAST. CONCLUSION: This research provides a transparent chain of evidence that derived clinically relevant competency standards for POCUS image interpretation.

State-of-the-art magnetic resonance imaging sequences for pediatric body imaging.

Longer examination time, need for anesthesia in smaller children and the inability of most children to hold their breath are major limitations of MRI in pediatric body imaging. Fortunately, with technical advances, many new and upcoming MRI sequences are overcoming these limitations. Advances in data acquisition and k-space sampling methods have enabled sequences with improved temporal and spatial resolution, and minimal artifacts. Sequences to minimize movement artifacts mainly utilize radial k-space filling, and examples include the stack-of-stars method for T1-weighted imaging and the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER)/BLADE method for T2-weighted imaging. Similarly, the sequences with improved temporal resolution and the ability to obtain multiple phases in a single breath-hold in dynamic imaging mainly use some form of partial k-space filling method. New sequences use a variable combination of data sampling methods like compressed sensing, golden-angle radial k-space filling, parallel imaging and partial k-space filling to achieve free-breathing, faster sequences that could be useful for pediatric abdominal and thoracic imaging. Simultaneous multi-slice method has improved diffusion-weighted imaging (DWI) with reduction in scan time and artifacts. In this review, we provide an overview of data sampling methods like parallel imaging, compressed sensing, radial k-space sampling, partial k-space sampling and simultaneous multi-slice. This is followed by newer available and upcoming sequences for T1-, T2- and DWI based on these other advances. We also discuss the Dixon method and newer approaches to reducing metal artifacts.

Clinical Feasibility of Structural and Functional MRI in Free-Breathing Neonates and Infants.

BACKGROUND: Evaluation of structural lung abnormalities with magnetic resonance imaging (MRI) has previously been shown to be predictive of clinical neonatal outcomes in preterm birth. MRI during free-breathing with phase-resolved functional lung (PREFUL) may allow for complimentary functional information without exogenous contrast. PURPOSE: To investigate the feasibility of structural and functional pulmonary MRI in a cohort of neonates and infants with no cardiorespiratory disease. Macrovascular pulmonary blood flows were also evaluated. STUDY TYPE: Prospective. POPULATION: Ten term infants with no clinically defined cardiorespiratory disease were imaged. Infants recruited from the general population and neonatal intensive care unit (NICU) were studied. FIELD STRENGTH/SEQUENCE: T1 -weighted VIBE, T2 -weighted BLADE uncorrected for motion. Ultrashort echo time (UTE) and 3D-flow data were acquired during free-breathing with self-navigation and retrospective reconstruction. Single slice 2D-gradient echo (GRE) images were acquired during free-breathing for PREFUL analysis. Imaging was performed at 3 T. ASSESSMENT: T1 , T2 , and UTE images were scored according to the modified Ochiai scheme by three pediatric body radiologists. Ventilation/perfusion-weighted maps were extracted from free-breathing GRE images using PREFUL analysis. Ventilation and perfusion defect percent (VDP, QDP) were calculated from the segmented ventilation and perfusion-weighted maps. Time-averaged cardiac blood velocities from three-dimensional-flow were evaluated in major pulmonary arteries and veins. STATISTICAL TEST: Intraclass correlation coefficient (ICC). RESULTS: The ICC of replicate structural scores was 0.81 (95% CI: 0.45-0.95) across three observers. Elevated Ochiai scores, VDP, and QDP were observed in two NICU participants. Excluding these participants, mean ± standard deviation structural scores were 1.2 ± 0.8, while VDP and QDP were 1.0% ± 1.1% and 0.4% ± 0.5%, respectively. Main pulmonary arterial blood flows normalized to body surface area were 3.15 ± 0.78 L/min/m2 . DATA CONCLUSION: Structural and functional pulmonary imaging is feasible using standard clinical MRI hardware (commercial whole-body 3 T scanner, table spine array, and flexible thoracic array) in free-breathing infants. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Liver magnetic resonance imaging: how we do it.

Magnetic resonance imaging is used for evaluating focal liver lesions, hepatic vascular diseases, biliary diseases and diffuse liver diseases in children. MRI examinations take a long time, often requiring sedation or anesthesia in smaller children. This makes it essential to understand the concepts and technique necessary to obtain an optimal examination for answering the clinical question while minimizing the need for sedation/anesthesia. We discuss key concepts including appropriate sequence selection, choice of contrast media, dynamic imaging, phases of contrast enhancement and protocol organization.

Solitary long-bone epiphyseal lesions in children: radiologic-pathological correlation and epidemiology.

BACKGROUND: Solitary epiphyseal lesions are rare and present with nonspecific imaging features. Knowledge regarding etiologies of pediatric epiphyseal lesions is limited to small studies. OBJECTIVE: The purpose of this study was to determine the relative incidence of pathologies affecting the pediatric epiphysis based on biopsy-proven cases with imaging. MATERIALS AND METHODS: We conducted a retrospective review of imaging studies including the terms "biopsy" or "resection" and entities known to affect the epiphysis and cross-referenced these with pathology reports, recording the relevant clinical data. Two radiologists performed comprehensive imaging review and recorded relevant features. RESULTS: Forty-nine children and adolescents met inclusion criteria. The long-bone epiphyseal lesion etiologies included chondroblastoma (n=22, 45%), nonspecific nonmalignant pathology (n=11, 22%), osteomyelitis (n=9, 18%), lymphoma (n=2, 4%) and 1 case of each of aneurysmal bone cyst, chondrosarcoma, enchondroma, hemangioendothelioma, and non-Langerhans cell histiocytosis. Median age was 13.1 years old (range 1.5-18.6 years). We performed comparative analysis of the two most common lesions in our series, chondroblastoma and osteomyelitis. Chondroblastoma was significantly more likely to be peripherally located (94% vs. 33%, P=0.002) and to demonstrate a discrete T1-weighted hypointense rim (94% vs. 33%, P=0.002); there were no significant differences in enhancement or intrinsic signal properties. Children with chondroblastoma were older (15.1 years vs. 7.3 years, P=0.001), and chondroblastoma lesions were significantly larger, with mean maximum lesion diameter of 25 mm (interquartile range [IQR] 20-30) vs. 12 mm (IQR 11-18) (P=0.001) and lesion volumes of 4.4 mL (IQR 2.4-7.9) vs. 0.4 mL (IQR 0.2-1.4) (P=0.01). CONCLUSION: This study reports the relative frequency of pathology of pediatric solitary epiphyseal lesions and describes several features that might assist in differentiating between chondroblastoma and osteomyelitis.

How to read a fetal magnetic resonance image 101.

Accurate antenatal diagnosis is essential for planning appropriate pregnancy management and improving perinatal outcomes. The provision of information vital for prognostication is a crucial component of prenatal imaging, and this can be enhanced by the use of fetal MRI. Image acquisition, interpretation and reporting of a fetal MR study can be daunting to the individual who has encountered few or none of these examinations. This article provides the radiology trainee with a general approach to interpreting a fetal MRI. The authors review the added value of prenatal MRI in the overall assessment of fetal wellbeing, discuss MRI protocols and techniques, and review the normal appearance of maternal and fetal anatomy. The paper concludes with a sample template for structured reporting, to serve as a checklist and guideline for reporting radiologists.

Functional MRI Safety and Artifacts during Deep Brain Stimulation: Experience in 102 Patients.

BackgroundWith growing numbers of patients receiving deep brain stimulation (DBS), radiologists are encountering these neuromodulation devices at an increasing rate. Current MRI safety guidelines, however, limit MRI access in these patients.PurposeTo describe an MRI (1.5 T and 3 T) experience and safety profile in a large cohort of participants with active DBS systems and characterize the hardware-related artifacts on images from functional MRI.Materials and MethodsIn this prospective study, study participants receiving active DBS underwent 1.5- or 3-T MRI (T1-weighted imaging and gradient-recalled echo [GRE]-echo-planar imaging [EPI]) between June 2017 and October 2018. Short- and long-term adverse events were tracked. The authors quantified DBS hardware-related artifacts on images from GRE-EPI (functional MRI) at the cranial coil wire and electrode contacts. Segmented artifacts were then transformed into standard space to define the brain areas affected by signal loss. Two-sample t tests were used to assess the difference in artifact size between 1.5- and 3-T MRI.ResultsA total of 102 participants (mean age ± standard deviation, 60 years ± 11; 65 men) were evaluated. No MRI-related short- and long-term adverse events or acute changes were observed. DBS artifacts were most prominent near the electrode contacts and over the frontoparietal cortical area where the redundancy of the extension wire is placed subcutaneously. The mean electrode contact artifact diameter was 9.3 mm ± 1.6, and 1.9% ± 0.8 of the brain was obscured by the coil artifact. The coil artifacts were larger at 3 T than at 1.5 T, obscuring 2.1% ± 0.7 and 1.4% ± 0.7 of intracranial volume, respectively (P < .001). The superficial frontoparietal cortex and deep structures neighboring the electrode contacts were most commonly obscured.ConclusionWith a priori local safety testing, patients receiving deep brain stimulation may safely undergo 1.5- and 3-T MRI. Deep brain stimulation hardware-related artifacts only affect a small proportion of the brain.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Martin in this issue.

Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor.

Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive ablative treatment for essential tremor. The size and location of therapeutic lesions producing the optimal clinical benefits while minimizing adverse effects are not known. We examined these relationships in patients with essential tremor undergoing MRgFUS. We studied 66 patients with essential tremor who underwent MRgFUS between 2012 and 2017. We assessed the Clinical Rating Scale for Tremor (CRST) scores at 3 months after the procedure and tracked the adverse effects (sensory, motor, speech, gait, and dysmetria) 1 day (acute) and 3 months after the procedure. Clinical data associated with the postoperative Day 1 lesions were used to correlate the size and location of lesions with tremor benefit and acute adverse effects. Diffusion-weighted imaging was used to assess whether acute adverse effects were related to lesions encroaching on nearby major white matter tracts (medial lemniscus, pyramidal, and dentato-rubro-thalamic). The area of optimal tremor response at 3 months after the procedure was identified at the posterior portion of the ventral intermediate nucleus. Lesions extending beyond the posterior region of the ventral intermediate nucleus and lateral to the lateral thalamic border were associated with increased risk of acute adverse sensory and motor effects, respectively. Acute adverse effects on gait and dysmetria occurred with lesions inferolateral to the thalamus. Lesions inferolateral to the thalamus or medial to the ventral intermediate nucleus were also associated with acute adverse speech effects. Diffusion-weighted imaging revealed that lesions associated with adverse sensory and gait/dysmetria effects compromised the medial lemniscus and dentato-rubro-thalamic tracts, respectively. Lesions associated with adverse motor and speech effects encroached on the pyramidal tract. Lesions larger than 170 mm3 were associated with an increased risk of acute adverse effects. Tremor improvement and acute adverse effects of MRgFUS for essential tremor are highly dependent on the location and size of lesions. These novel findings could refine current MRgFUS treatment planning and targeting, thereby improving clinical outcomes in patients.

Prominent Inferior Intercavernous Sinus on Sagittal T1-Weighted Images: A Sign of Intracranial Hypotension.

OBJECTIVE: The purpose of this study is to describe the diagnostic accuracy of the dilatation of the inferior intercavernous sinus as a sign of intracranial hypotension and to raise awareness of this anatomic structure, which can be mistaken for a focal pituitary lesion. MATERIALS AND METHODS: Sagittal T1-weighted images of 26 patients with intracranial hypotension and 28 control subjects were evaluated to determine the presence of a distended inferior intercavernous sinus. Information about the shape, size, and signal of the inferior intercavernous sinus was also collected. The chi-square test was used to compare both groups. Sensitivity and specificity of the dilatation of the inferior intercavernous sinus as a sign of intracranial hypotension were calculated. RESULTS: A visible inferior intercavernous sinus was found in 13 of 26 patients with intracranial hypotension (50%) and in four of 28 control subjects (14.3%). These percentages were significantly different (p = 0.005). There was no significant difference in size of the inferior intercavernous sinus in the intracranial hypotension group (median, 5.86 mm(2); interquartile range, 6.28 mm(2)) compared with the control group (median, 8.25 mm(2); interquartile range, 16.69 mm(2)). Changes in the size of the inferior intercavernous sinus were detected in congruence with the appearance or resolution of intracranial hypotension. CONCLUSION: Dilatation of the inferior intercavernous sinus is frequently associated with intracranial hypotension, although it can also be found in the healthy adult as a normal anatomic variant. Recognition of this anatomic structure is important to avoid mistaking it for a focal pituitary lesion.

Subpleural pulmonary cysts in children: Associations beyond Trisomy 21.

BACKGROUND: Small air-filled peripheral subpleural cysts are a well-described feature of pulmonary anatomy at computerized tomographic (CT) scan in children with Trisomy 21, yet only anecdotally described in association with other pathologies. The significance of these cysts is unknown. OBJECTIVE: To investigate and explore the pathogenesis of these subpleural cysts in children. MATERIALS AND METHODS: A retrospective review of 16 cases with subpleural cysts diagnosed on CT chest was performed. The distribution, location, and ancillary CT findings were recorded. Hospital charts were reviewed for clinical details, especially cardiac abnormalities, pulmonary artery hypertension (PAH) and genetic associations. Histopathological and clinical correlative data were recorded. RESULTS: Eleven of the 16 children (69%) were found to have an underlying chromosomal or genetic abnormality, six of whom had Trisomy 21. The remaining 5 of the 16 cases (21%) had miscellaneous disorders without an identifiable genetic basis. The most common co-morbidities were cardiac abnormalities (81%) and PAH (62.5%). Regardless of their underlying etiologies, the cysts were present bilaterally in most cases (14/16, 88%). We observed both the postnatal development and the progression of cysts in our cohort. On long-term follow-up, there were five deaths (31%) and six cases (38%) requiring maintenance oxygen therapy due to chronic hypoxia. Two cases (12.5%) became completely asymptomatic after correction of their underlying abnormalities. CONCLUSION: Subpleural cysts are not exclusive to Trisomy 21 and may be seen in other inherited or acquired causes, likely due to altered alveolar growth. We suspect these cysts are a sign of an underlying developmental disorder with variable clinical effect, especially in children with congenital cardiac disease.

Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency.

Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion-deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10-100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in 'immunologically cold' tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy.

Mapping efficacious deep brain stimulation for pediatric dystonia.

OBJECTIVE: The objective of this study was to report the authors' experience with deep brain stimulation (DBS) of the internal globus pallidus (GPi) as a treatment for pediatric dystonia, and to elucidate substrates underlying clinical outcome using state-of-the-art neuroimaging techniques. METHODS: A retrospective analysis was conducted in 11 pediatric patients (6 girls and 5 boys, mean age 12 ± 4 years) with medically refractory dystonia who underwent GPi-DBS implantation between June 2009 and September 2017. Using pre- and postoperative MRI, volumes of tissue activated were modeled and weighted by clinical outcome to identify brain regions associated with clinical outcome. Functional and structural networks associated with clinical benefits were also determined using large-scale normative data sets. RESULTS: A total of 21 implanted leads were analyzed in 11 patients. The average follow-up duration was 19 ± 20 months (median 5 months). Using a 7-point clinical rating scale, 10 patients showed response to treatment, as defined by scores < 3. The mean improvement in the Burke-Fahn-Marsden Dystonia Rating Scale motor score was 40% ± 23%. The probabilistic map of efficacy showed that the voxel cluster most associated with clinical improvement was located at the posterior aspect of the GPi, comparatively posterior and superior to the coordinates of the classic GPi target. Strong functional and structural connectivity was evident between the probabilistic map and areas such as the precentral and postcentral gyri, parietooccipital cortex, and brainstem. CONCLUSIONS: This study reported on a series of pediatric patients with dystonia in whom GPi-DBS resulted in variable clinical benefit and described a clinically favorable stimulation site for this cohort, as well as its structural and functional connectivity. This information could be valuable for improving surgical planning, simplifying programming, and further informing disease pathophysiology.

Predicting optimal deep brain stimulation parameters for Parkinson's disease using functional MRI and machine learning.

Commonly used for Parkinson's disease (PD), deep brain stimulation (DBS) produces marked clinical benefits when optimized. However, assessing the large number of possible stimulation settings (i.e., programming) requires numerous clinic visits. Here, we examine whether functional magnetic resonance imaging (fMRI) can be used to predict optimal stimulation settings for individual patients. We analyze 3 T fMRI data prospectively acquired as part of an observational trial in 67 PD patients using optimal and non-optimal stimulation settings. Clinically optimal stimulation produces a characteristic fMRI brain response pattern marked by preferential engagement of the motor circuit. Then, we build a machine learning model predicting optimal vs. non-optimal settings using the fMRI patterns of 39 PD patients with a priori clinically optimized DBS (88% accuracy). The model predicts optimal stimulation settings in unseen datasets: a priori clinically optimized and stimulation-naïve PD patients. We propose that fMRI brain responses to DBS stimulation in PD patients could represent an objective biomarker of clinical response. Upon further validation with additional studies, these findings may open the door to functional imaging-assisted DBS programming.

Network Basis of Seizures Induced by Deep Brain Stimulation: Literature Review and Connectivity Analysis.

BACKGROUND: Whereas transient, self-limiting seizures are an infrequent but known complication of deep brain stimulation (DBS) implantation surgery, stimulation itself has occasionally been reported to result in seizure activity at delayed time points. The neural circuitry implicated in stimulation-induced seizures is unknown. CASE DESCRIPTION: A 47-year-old woman underwent chronic subcallosal cingulate DBS for treatment of refractory anorexia nervosa and experienced seizure with stimulation onset. Supratherapeutic voltage caused a generalized seizure. The patient subsequently experienced a full recovery. We reviewed the literature for other cases of delayed postoperative DBS seizures associated with stimulation. We also investigated whether the higher voltage may have recruited networks implicated in epilepsy. The supratherapeutic voltage stimulated a larger area and engaged vulnerable networks, including bilateral hippocampi, cingulate gyrus, and temporal lobes. Literature review identified 20 studies reporting delayed seizure after DBS surgery, 13 of which demonstrated a robust association with mostly nonmotor DBS stimulation. CONCLUSIONS: Nonmotor DBS targets, particularly in patients with epilepsy, may be more vulnerable to stimulation-induced seizures; as such, extra caution should be used when programming stimulation parameters at these DBS targets.

3-Tesla MRI of deep brain stimulation patients: safety assessment of coils and pulse sequences.

OBJECTIVE: Physicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients' accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research. METHODS: A phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from "the worst" to "the most common."In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed. RESULTS: In the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event. CONCLUSIONS: Under the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.