Clinical utility of arterial spin labeling imaging in disorders of the nervous system.

Neuroimaging is an indispensable tool in the workup and management of patients with neurological disorders. Arterial spin labeling (ASL) is an imaging modality that permits the examination of blood flow and perfusion without the need for contrast injection. Noninvasive in nature, ASL provides a feasible alternative to existing vascular imaging techniques, including angiography and perfusion imaging. While promising, ASL has yet to be fully incorporated into the diagnosis and management of neurological disorders. This article presents a review of the most recent literature on ASL, with a special focus on its use in moyamoya disease, brain neoplasms, seizures, and migraines and a commentary on recent advances in ASL that make the imaging technique more attractive as a clinically useful tool.

Contemporary and emerging magnetic resonance imaging methods for evaluation of moyamoya disease.

Numerous recent technological advances offer the potential to substantially enhance the MRI evaluation of moyamoya disease (MMD). These include high-resolution volumetric imaging, high-resolution vessel wall characterization, improved cerebral angiographic and perfusion techniques, high-field imaging, fast scanning methods, and artificial intelligence. This review discusses the current state-of-the-art MRI applications in these realms, emphasizing key imaging findings, clinical utility, and areas that will benefit from further investigation. Although these techniques may apply to imaging of a wide array of neurovascular or other neurological conditions, consideration of their application to MMD is useful given the comprehensive multidimensional MRI assessment used to evaluate MMD. These MRI techniques span from basic cross-sectional to advanced functional sequences, both qualitative and quantitative.The aim of this review was to provide a comprehensive summary and analysis of current key relevant literature of advanced MRI techniques for the evaluation of MMD with image-rich case examples. These imaging methods can aid clinical characterization, help direct treatment, assist in the evaluation of treatment response, and potentially improve the understanding of the pathophysiology of MMD.

Sports-related brain injuries: connecting pathology to diagnosis.

Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery.

Evaluation and treatment of children with radiation-induced cerebral vasculopathy.

OBJECTIVE: Stenoocclusive cerebral vasculopathy is an infrequent delayed complication of ionizing radiation. It has been well described with photon-based radiation therapy but less so following proton-beam radiotherapy. The authors report their recent institutional experience in evaluating and treating children with radiation-induced cerebral vasculopathy. METHODS: Eligible patients were age 21 years or younger who had a history of cranial radiation and subsequently developed vascular narrowing detected by MR arteriography that was significant enough to warrant cerebral angiography, with or without ischemic symptoms. The study period was January 2011 to March 2019. RESULTS: Thirty-one patients met the study inclusion criteria. Their median age was 12 years, and 18 (58%) were male. Proton-beam radiation therapy was used in 20 patients (64.5%) and photon-based radiation therapy was used in 11 patients (35.5%). Patients were most commonly referred for workup as a result of incidental findings on surveillance tumor imaging (n = 23; 74.2%). Proton-beam patients had a shorter median time from radiotherapy to catheter angiography (24.1 months [IQR 16.8-35.4 months]) than patients who underwent photon-based radiation therapy (48.2 months [IQR 26.6-61.1 months]; p = 0.04). Eighteen hemispheres were revascularized in 15 patients. One surgical patient suffered a contralateral hemispheric infarct 2 weeks after revascularization; no child treated medically (aspirin) has had a stroke to date. The median follow-up duration was 29.2 months (IQR 21.8-54.0 months) from the date of the first catheter angiogram to last clinic visit. CONCLUSIONS: All children who receive cranial radiation therapy from any source, particularly if the parasellar region was involved and the child was young at the time of treatment, require close surveillance for the development of vasculopathy. A structured and detailed evaluation is necessary to determine optimal treatment.

Arterial spin labeling perfusion changes of the frontal lobes in children with posterior fossa syndrome.

OBJECTIVE: Posterior fossa syndrome (PFS) is a common complication following the resection of posterior fossa tumors in children. The pathophysiology of PFS remains incompletely elucidated; however, the wide-ranging symptoms of PFS suggest the possibility of widespread cortical dysfunction. In this study, the authors utilized arterial spin labeling (ASL), an MR perfusion modality that provides quantitative measurements of cerebral blood flow without the use of intravenous contrast, to assess cortical blood flow in patients with PFS. METHODS: A database of medulloblastoma treated at the authors' institution from 2004 to 2016 was retrospectively reviewed, and 14 patients with PFS were identified. Immediate postoperative ASL for patients with PFS and medulloblastoma patients who did not develop PFS were compared. Additionally, in patients with PFS, ASL following the return of speech was compared with immediate postoperative ASL. RESULTS: On immediate postoperative ASL, patients who subsequently developed PFS had statistically significant decreases in right frontal lobe perfusion and a trend toward decreased perfusion in the left frontal lobe compared with controls. Patients with PFS had statistically significant increases in bilateral frontal lobe perfusion after the resolution of symptoms compared with their immediate postoperative imaging findings. CONCLUSIONS: ASL perfusion imaging identifies decreased frontal lobe blood flow as a strong physiological correlate of PFS that is consistent with the symptomatology of PFS. This is the first study to demonstrate that decreases in frontal lobe perfusion are present in the immediate postoperative period and resolve with the resolution of symptoms, suggesting a physiological explanation for the transient symptoms of PFS.

Ferumoxytol-enhanced MRI for surveillance of pediatric cerebral arteriovenous malformations.

OBJECTIVE: Children with intracranial arteriovenous malformations (AVMs) undergo digital DSA for lesion surveillance following their initial diagnosis. However, DSA carries risks of radiation exposure, particularly for the growing pediatric brain and over lifetime. The authors evaluated whether MRI enhanced with a blood pool ferumoxytol (Fe) contrast agent (Fe-MRI) can be used for surveillance of residual or recurrent AVMs. METHODS: A retrospective cohort was assembled of children with an established AVM diagnosis who underwent surveillance by both DSA and 3-T Fe-MRI from 2014 to 2016. Two neuroradiologists blinded to the DSA results independently assessed Fe-enhanced T1-weighted spoiled gradient recalled acquisition in steady state (Fe-SPGR) scans and, if available, arterial spin labeling (ASL) perfusion scans for residual or recurrent AVMs. Diagnostic confidence was examined using a Likert scale. Sensitivity, specificity, and intermodality reliability were determined using DSA studies as the gold standard. Radiation exposure related to DSA was calculated as total dose area product (TDAP) and effective dose. RESULTS: Fifteen patients were included in this study (mean age 10 years, range 3-15 years). The mean time between the first surveillance DSA and Fe-MRI studies was 17 days (SD 47). Intermodality agreement was excellent between Fe-SPGR and DSA (κ = 1.00) but poor between ASL and DSA (κ = 0.53; 95% CI 0.18-0.89). The sensitivity and specificity for detecting residual AVMs using Fe-SPGR were 100% and 100%, and using ASL they were 72% and 100%, respectively. Radiologists reported overall high diagnostic confidence using Fe-SPGR. On average, patients received two surveillance DSA studies over the study period, which on average equated to a TDAP of 117.2 Gy×cm2 (95% CI 77.2-157.4 Gy×cm2) and an effective dose of 7.8 mSv (95% CI 4.4-8.8 mSv). CONCLUSIONS: Fe-MRI performed similarly to DSA for the surveillance of residual AVMs. Future multicenter studies could further investigate the efficacy of Fe-MRI as a noninvasive alternative to DSA for monitoring AVMs in children.

Cerebral blood flow in children with syndromic craniosynostosis: cohort arterial spin labeling studies.

OBJECTIVE: In comparison with the general population, children with syndromic craniosynostosis (sCS) have abnormal cerebral venous anatomy and are more likely to develop intracranial hypertension. To date, little is known about the postnatal development change in cerebral blood flow (CBF) in sCS. The aim of this study was to determine CBF in patients with sCS, and compare findings with control subjects. METHODS: A prospective cohort study of patients with sCS using MRI and arterial spin labeling (ASL) determined regional CBF patterns in comparison with a convenience sample of control subjects with identical MRI/ASL assessments in whom the imaging showed no cerebral/neurological pathology. Patients with SCS and control subjects were stratified into four age categories and compared using CBF measurements from four brain lobes, the cerebellum, supratentorial cortex, and white matter. In a subgroup of patients with sCS the authors also compared longitudinal pre- to postoperative CBF changes. RESULTS: Seventy-six patients with sCS (35 female [46.1%] and 41 male [53.9%]), with a mean age of 4.5 years (range 0.2-19.2 years), were compared with 86 control subjects (38 female [44.2%] and 48 male [55.8%]), with a mean age of 6.4 years (range 0.1-17.8 years). Untreated sCS patients < 1 year old had lower CBF than control subjects. In older age categories, CBF normalized to values observed in controls. Graphical analyses of CBF by age showed that the normally expected peak in CBF during childhood, noted at 4 years of age in control subjects, occurred at 5-6 years of age in patients with sCS. Patients with longitudinal pre- to postoperative CBF measurements showed significant increases in CBF after surgery. CONCLUSIONS: Untreated patients with sCS < 1 year old have lower CBF than control subjects. Following vault expansion, and with age, CBF in these patients normalizes to that of control subjects, but the usual physiological peak in CBF in childhood occurs later than expected.

Arterial spin-labeling cerebral perfusion changes after revascularization surgery in pediatric moyamoya disease and syndrome.

OBJECTIVE: Moyamoya disease is a dynamic cerebrovascular condition that often requires vascular surveillance. Arterial spin labeling (ASL) is an MR perfusion method that is increasingly used for stroke and other various neurovascular pathologies. Unlike perfusion-weighted MRI, ASL uses endogenous water molecules for signal and therefore obviates gadolinium use; and provides direct, not relative, quantitative cerebral blood flow (CBF) measures. Presently, the potential role of ASL for evaluating postoperative pediatric moyamoya patients is relatively unexplored. This study investigated the role for ASL in evaluating cerebral hemodynamic changes in children who underwent revascularization surgery. METHODS: This retrospective study examined 15 consecutive pediatric patients with moyamoya disease (n = 7) or moyamoya syndrome (n = 8) presenting between 2010 and 2014 who underwent revascularization and in whom 3T ASL was performed pre- and postoperatively. Postoperative MRI at least 3 months after revascularization procedure was used for analysis. Quantitative CBF in various vascular territories was interrogated: anterior, middle, and posterior cerebral arteries, and basal ganglia supplied by the lenticulostriate collaterals, resulting in evaluation of 20 brain regions. RESULTS: After revascularization, CBF in the high middle cerebral artery territory significantly increased (p = 0.0059), accompanied by a decrease in CBF to the ipsilateral lenticulostriate-supplied basal ganglia (p = 0.0053). No perfusion changes occurred in the remaining cerebral vascular territories after surgery. CONCLUSIONS: ASL-based quantitative CBF showed improved cerebral perfusion to the middle cerebral artery territory after revascularization in children with both moyamoya syndrome and disease. Reduced perfusion to the basal ganglia might reflect pruning of the lenticulostriate collaterals, potentially from effects of revascularization. ASL can quantitatively evaluate hemodynamic changes in children with moyamoya after revascularization, and it may be a useful adjunct to routine clinical MRI surveillance.

A perfusion territory shift attributable solely to the secondary collaterals in moyamoya patients: a potential risk factor for preoperative hemorrhagic stroke revealed by t-ASL and 3D-TOF-MRA.

OBJECTIVE: The authors conducted a study to noninvasively and nonradioactively reveal moyamoya disease (MMD) intracerebral perfusion and perfusion territory supplied by the unilateral internal carotid artery (ICA) and external carotid artery (ECA) and bilateral vertebral arteries (VAs) before surgery and to further identify risk factors for preoperative hemorrhage in adult MMD. METHODS: Forty-three consecutive adult patients with bilateral MMD underwent unenhanced T1-weighted MRI, territorial arterial spin labeling (t-ASL), and unenhanced 3D time-of-flight MRA (3D-TOF-MRA). Clinical factors, including age, sex, hypertension, diabetes mellitus, hyperlipidemia, current smoking status, and history of taking aspirin, were gathered and stratified. Univariate logistic regression analyses were used to examine the relationship between various risk factors and the occurrence of preoperative hemorrhage. Stepwise multivariate logistic regression analyses were used to determine independent risk factors of preoperative hemorrhage in MMD. RESULTS: Among the 86 MMD hemispheres, t-ASL revealed 137 perfusion territory shifts in 79 hemispheres. Five distinct categories of perfusion territory shifts were observed on t-ASL maps. The subtypes of perfusion territory shift on t-ASL maps were further subdivided into 2 different categories, group A and group B, in combination with findings on 3D-TOF-MRA. A perfusion territory shift attributable solely to the secondary collaterals was a potential independent risk factor for preoperative hemorrhage (p = 0.026; 95% CI 1.201-18.615; OR 4.729). After eliminating the influence of the secondary collaterals, the primary collaterals had no significant effect on the risk of preoperative hemorrhage (p = 0.182). CONCLUSIONS: t-ASL could reveal comprehensive MMD cerebral blood perfusion and the vivid perfusion territory shifts fed by the unilateral ICA and ECA and bilateral VAs in a noninvasive, straightforward, nonradioactive, and nonenhanced manner. 3D-TOF-MRA could subdivide t-ASL perfusion territory shifts according to their shunt arteries. A perfusion territory shift attributable to the secondary collaterals is a potential independent risk factor for preoperative hemorrhage in MMD patients. A perfusion territory shift fed by the primary collaterals may not have a strong effect on preoperative hemorrhage in MMD patients. These findings make the combined modalities of t-ASL and 3D-TOF-MRA a feasible tool for MMD disease assessment, management, and surgical strategy planning.

Association of cognitive function with cerebral blood flow in children with moyamoya disease.

OBJECTIVE: The cognitive effects of main cerebral artery occlusive lesions are unclear in children with moyamoya disease (MMD). The authors aimed to investigate cognitive function in the presurgical phase of pediatric patients with MMD with no apparent brain lesions. METHODS: In this prospective, observational, single-center study, 21 children (mean age 10 ± 3.0 years, range 5-14 years) diagnosed with MMD at Hokkaido University Hospital between 2012 and 2018 were enrolled. A cross-sectional evaluation of intellectual ability was performed using the Wechsler Intelligence Scale for Children-Fourth Edition at the initial diagnosis. rCBF was measured using [123I] N-isopropyl p-iodoamphetamine/SPECT. The associations among clinical factors, disease severity, regional cerebral blood flow (rCBF), and intelligence test scores were also examined. RESULTS: The mean full-scale intelligence quotient (FIQ) was 101.8 ± 12.5 (range 76-125) in children with no apparent brain lesions. A significant difference in the intelligence scale index score was observed, most frequently (42.9%) between working memory index (WMI) and verbal comprehension index (VCI; VCI - WMI > 11 points). Regional CBF was significantly reduced both in the left and right medial frontal cortices (left: 61.3 ± 5.3 ml/100 g/min, right 65.3 ± 5.3 ml/100 g/min; p < 0.001) compared to the cerebellum (77.8 ± 6.8 ml/100 g/min). There was a significant association of rCBF in the left dorsolateral prefrontal cortex (DLPFC) with FIQ (r = 0.46, p = 0.034), perceptual reasoning index (PRI; r = 0.44, p = 0.045), and processing speed index (PSI; r = 0.44, p = 0.045). There was an association between rCBF of the left medial frontal cortex and PSI (r = 0.49, p = 0.026). Age of onset, family history, ischemic symptoms, and angiographic severity were not associated with poor cognitive performance. CONCLUSIONS: Although average intellectual ability was not reduced in children with MMD, the association of reduced rCBF in the left DLPFC and medial frontal cortex with FIQ, PRI, and PSI suggests mild cognitive dysfunction due to cerebral hypoperfusion.

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.

High-resolution 3D volumetric contrast-enhanced MR angiography with a blood pool agent (ferumoxytol) for diagnostic evaluation of pediatric brain arteriovenous malformations.

OBJECTIVE Patients with brain arteriovenous malformations (AVMs) often require repeat imaging with MRI or MR angiography (MRA), CT angiography (CTA), and digital subtraction angiography (DSA). The ideal imaging modality provides excellent vascular visualization without incurring added risks, such as radiation exposure. The purpose of this study is to evaluate the performance of ferumoxytol-enhanced MRA using a high-resolution 3D volumetric sequence (fe-SPGR) for visualizing and grading pediatric brain AVMs in comparison with CTA and DSA, which is the current imaging gold standard. METHODS In this retrospective cohort study, 21 patients with AVMs evaluated by fe-SPGR, CTA, and DSA between April 2014 and August 2017 were included. Two experienced raters graded AVMs using Spetzler-Martin criteria on all imaging studies. Lesion conspicuity (LC) and diagnostic confidence (DC) were assessed using a 5-point Likert scale, and interrater agreement was determined. The Kruskal-Wallis test was performed to assess the raters' grades and scores of LC and DC, with subsequent post hoc pairwise comparisons to assess for statistically significant differences between pairs of groups at p < 0.05. RESULTS Assigned Spetzler-Martin grades for AVMs on DSA, fe-SPGR, and CTA were not significantly different (p = 0.991). LC and DC scores were higher with fe-SPGR than with CTA (p < 0.05). A significant difference in LC scores was found between CTA and fe-SPGR (p < 0.001) and CTA and DSA (p < 0.001) but not between fe-SPGR and DSA (p = 0.146). A significant difference in DC scores was found among DSA, fe-SPGR, and CTA (p < 0.001) and between all pairs of the groups (p < 0.05). Interrater agreement was good to very good for all image groups (κ = 0.77-1.0, p < 0.001). CONCLUSIONS Fe-SPGR performed robustly in the diagnostic evaluation of brain AVMs, with improved visual depiction of AVMs compared with CTA and comparable Spetzler-Martin grading relative to CTA and DSA.

Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome.

OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO2 challenge and blood oxygen level-dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). RESULTS Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. CONCLUSIONS Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS.

Arterial spin labeling magnetic resonance imaging: toward noninvasive diagnosis and follow-up of pediatric brain arteriovenous malformations.

OBJECT Arterial spin labeling (ASL)-MRI is becoming a routinely used sequence for ischemic strokes, as it quantifies cerebral blood flow (CBF) without the need for contrast injection. As brain arteriovenous malformations (AVMs) are highflow vascular abnormalities, increased CBF can be identified inside the nidus or draining veins. The authors aimed to analyze the relevance of ASL-MRI in the diagnosis and follow-up of children with brain AVM. METHODS The authors performed a retrospective analysis of 21 patients who had undergone digital subtraction angiography (DSA) and pseudo-continuous ASL-MRI for the diagnosis or follow-up of brain AVM after radiosurgery or embolization. They compared the AVM nidus location between ASL-MRI and 3D contrast-enhanced T1 MRI, as well as the CBF values obtained in the nidus (CBFnidus) and the normal cortex (CBFcortex) before and after treatment. RESULTS The ASL-MRI correctly demonstrated the nidus location in all cases. Nidal perfusion (mean CBFnidus 137.7 ml/100 mg/min) was significantly higher than perfusion in the contralateral normal cortex (mean CBFcortex 58.6 ml/100 mg/min; p < 0.0001, Mann-Whitney test). Among 3 patients followed up after embolization, a reduction in both AVM size and CBF values was noted. Among 5 patients followed up after radiosurgery, a reduction in the nidus size was observed, whereas CBFnidus remained higher than CBFcortex. CONCLUSIONS In this study, ASL-MRI revealed nidus location and patency after treatment thanks to its ability to demonstrate focal increased CBF values. Absolute quantification of CBF values could be relevant in the follow-up of pediatric brain AVM after partial treatment, although this must be confirmed in larger prospective trials.

Medullary hemangioblastoma in a child with von Hippel-Lindau disease: vascular tumor perfusion depicted by arterial spin labeling and dynamic contrast-enhanced imaging.

Medullary hemangioblastoma is very rare in children. Based on small nodular enhancement with peritumoral edema and without dilated feeding arteries on conventional MRI, hemangioblastoma, pilocytic astrocytoma, oligodendroglioma, and ganglioglioma were included in the differential diagnosis of the medullary tumor. In this case report, the authors emphasize the diagnostic value of arterial spin labeling and dynamic contrast-enhanced MRI in demonstrating vascular tumor perfusion of hemangioblastoma in a 12-year-old boy who was later found to have von Hippel-Lindau disease.