Anything but Little: a Pictorial Review on Anatomy and Pathology of the Cerebellum.

Despite its small size the cerebellum is an anatomically complex and functionally important part of the brain. Traditionally the cerebellum is viewed as a motor control structure entirely devoted to motor control and learning, but recent functional magnetic resonance imaging (fMRI) studies demonstrated significant involvement of the cerebellum in higher order cognitive functions. The anatomical complexity of the cerebellum is reflected by the several nomenclature systems that exist for the description of cerebellar anatomy. The cerebellum can be affected by a variety of pathological processes, including congenital, infectious and inflammatory, neoplastic, vascular, degenerative and toxic metabolic diseases. The purpose of this pictorial review is to (1) provide a general overview of cerebellar anatomy and function, (2) demonstrate normal cerebellar anatomy on imaging studies, and (3) illustrate both common as well as rare pathological conditions affecting the cerebellum.

First Evidence of Activity of Enfortumab Vedotin on Brain Metastases in Urothelial Cancer Patients.

Enfortumab vedotin (EV), an antibody-drug conjugate directed against Nectin-4, significantly prolonged survival compared to standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The overall response rate in the phase 3 EV301 trial leading to approval was 40.6%. However, no data have been published yet regarding the effect of EV on brain metastases. Here, we present three patients from different centers with brain metastases receiving EV. A 58-year-old white male patient, who had been heavily pretreated for urothelial carcinoma with visceral metastases and a solitary clinically active brain metastasis, started on EV 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle. After three cycles, the first evaluation showed a partial remission by RECIST v1.1, with a near complete response on the brain metastasis and disappearance of neurological symptoms. The patient is currently still receiving EV. A second, 74-year-old male patient started on the same regimen, after previous progression on platinum-based chemotherapy and avelumab in maintenance. The patient achieved a complete response and received therapy for five months. Nevertheless, therapy was discontinued at the patient's request. Shortly after, he developed new leptomeningeal metastases. Upon rechallenge with EV, there was a significant reduction in the diffuse meningeal infiltration. A third, 50-year-old white male patient also received EV after previous progression on cisplatin-gemcitabine and atezolizumab maintenance, followed by palliative whole-brain radiotherapy and two cycles of vinflunine. After three cycles of EV, there was a significant reduction in the brain metastases. The patient is currently still receiving EV. These are the first reports on the efficacy of EV in patients with urothelial carcinoma and active brain metastases.

Acute interstitial nephritis manifesting as a persistent nephogram.

We report a case of a 61-year-old woman who presented to the emergency department with high inflammatory parameters and acute renal failure. Marked enlarged kidneys with persistent nephrogram were found on contrast-enhanced computed tomography . Renal biopsy showed acute interstitial nephritis. Acute interstitial nephritis must be included in the differential diagnosis in patients presenting with a persistent nephrogram.

Spinal Non-Hodgkin Lymphoma Mimicking Epidural Hematoma.

A patient, recently diagnosed with non-Hodgkin lymphoma, presented with acute tetraplegia after surgical cervical lymph node biopsy. MRI of the cervical spine demonstrated an epidural space-occupying lesion with compressive myelopathy. While epidural hematoma was the tentative diagnosis, intra-operatively non-Hodgkin lymphoma was found. Several factors may have accounted for the inaccurate interpretation of the MRI: the acute clinical presentation appearing shortly after surgery, the non-specific signal intensities of (hyper-) acute hematomas, the lack of contrast-enhanced images, and the absence of the FDG-avid spinal mass in the PET/CT-report. Without radiological features of invasiveness and contrast-enhanced images, careful interpretation is mandatory for space-occupying epidural lesions. Teaching Point: Caution is needed when interpreting an epidural space-occupying lesion in the absence of contrast-enhanced images.

Distinctive diffusion-weighted imaging features in late-onset genetic leukoencephalopathies.

Genetic leukoencephalopathies are inherited disorders characterized by progressive white matter involvement. Although most are paediatric conditions, late-onset adult leukoencephalopathies are being increasingly recognized. Adult leukoencephalopathies may present as neurodegenerative diseases with cognitive decline and motor symptoms. Similar to their paediatric counterparts, different adult leukoencephalopathies often have distinctive MRI appearances. In particular, DWI has been recently shown to demonstrate specific patterns of persistent diffusion restriction in several adult-onset leukoencephalopathies. As such, DWI may provide important clues to the diagnosis of adult-onset leukoencephalopathy. The purpose of this review is to discuss characteristic DWI features in some late-onset leukoencephalopathies.

Neuroradiological findings in three cases of pontocerebellar hypoplasia type 9 due to AMPD2 mutation: typical MRI appearances and pearls for differential diagnosis.

Pontocerebellar hypoplasia type 9 (PCH9) is a rare autosomal recessive neurodegenerative disorder with prenatal onset caused by mutations in adenosine monophosphate deaminase 2 (AMPD2). PCH9 patients demonstrate severe neurodevelopmental delay with early onset and typical magnetic resonance imaging (MRI) findings consisting in: pontine hypoplasia or atrophy with dragonfly cerebellar atrophy appearance on coronal images, reduction in size of the pons and middle cerebellar peduncles, abnormal midbrain describing a figure of "8" on axial images, diffuse loss of cerebral white matter with striking periventricular leukomalacia (PVL), and absence or extreme thinning of the corpus callosum. A review of the literature on PCH9 shows that the MRI phenotype observed in the series herein presented is similar to the eleven cases of PCH9 previously reported. Finally, the main radiological elements which differentiate this diagnosis from other PCH subtypes are described.

Current concepts in radiologic assessment of pediatric brain tumors during treatment, part 1.

Pediatric brain tumors differ from those in adults by location, phenotype and genotype. In addition, they show dissimilar imaging characteristics before and after treatment. While adult brain tumor treatment effects are primarily assessed on MRI by measuring the contrast-enhancing components in addition to abnormalities on T2-weighted and fluid-attenuated inversion recovery images, these methods cannot be simply extrapolated to pediatric central nervous system tumors. A number of researchers have attempted to solve the problem of tumor assessment during treatment in pediatric neuro-oncology; specifically, the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group was recently established to deal with the distinct challenges in evaluating treatment-related changes on imaging, but no established criteria are available. In this article we review the current methods to evaluate brain tumor therapy and the numerous challenges that remain. In part 1, we examine the role of T2-weighted imaging and fluid-attenuated inversion recovery sequences, contrast enhancement, volumetrics and diffusion imaging techniques. We pay particular attention to several specific pediatric brain tumors, such as optic pathway glioma, diffuse midline glioma and medulloblastoma. Finally, we review the best means to assess leptomeningeal seeding.

Clinical vascular imaging in the brain at 7T.

Stroke and related cerebrovascular diseases are a major cause of mortality and disability. Even at standard-field-strengths (1.5T), MRI is by far the most sensitive imaging technique to detect acute brain infarctions and to characterize incidental cerebrovascular lesions, such as white matter hyperintensities, lacunes and microbleeds. Arterial time-of-flight (TOF) MR angiography (MRA) can depict luminal narrowing or occlusion of the major brain feeding arteries, and this without the need for contrast administration. Compared to 1.5T MRA, the use of high-field strength (3T) and even more so ultra-high-field strengths (7T), enables the visualization of the lumen of much smaller intracranial vessels, while adding a contrast agent to TOF MRA at 7T may enable the visualization of even more distal arteries in addition to veins and venules. Moreover, with 3T and 7T, the arterial vessel walls beyond the circle of Willis become visible with high-resolution vessel wall imaging. In addition, with 7T MRI, the brain parenchyma can now be visualized on a submillimeter scale. As a result, high-resolution imaging studies of the brain and its blood supply at 7T have generated new concepts of different cerebrovascular diseases. In the current article, we will discuss emerging clinical applications and future directions of vascular imaging in the brain at 7T MRI.

Do Lacunar Infarcts Have Different Aetiologies? Risk Factor Profiles of Lacunar Infarcts in Deep White Matter and Basal Ganglia: The Second Manifestations of ARTerial Disease-Magnetic Resonance Study.

BACKGROUND: Evidence suggests that lacunar infarcts have different etiologies, possibly related to their anatomical location and vascular territory. We investigated the risk factor profiles of patients with new lacunar infarcts in the basal ganglia and deep white matter. METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study, a prospective cohort on brain changes on MRI in patients with symptomatic atherosclerotic disease, 679 patients (57 ± 9 years) had vascular screening and MRI at baseline and after a mean follow-up of 3.9 years. We investigated the association between vascular risk factors at baseline and appearance of new lacunar infarcts in the basal ganglia and deep white matter at follow-up. RESULTS: New lacunar infarcts appeared in 44 patients in the basal ganglia and in 37 patients in the deep white matter. In multivariable analysis, older age, history of cerebrovascular disease, and baseline white matter hyperintensity (WMH) volume were associated with increased risk of new lacunar infarcts in both locations. Hyperhomocysteinemia was associated with increased risk of lacunar infarcts in the basal ganglia (relative risk [RR] 2.0; 95% CI 1.0-4.2), whereas carotid stenosis >70% (RR 2.5; 95% CI 1.2-5.0), smoking (per 10 pack-year: RR 1.1; 95% CI 1.0-1.3), hypertension (RR 3.4; 95% CI 1.2-9.7), and progression of WMH volume (RR 2.4; 95% CI 1.1-5.2) were associated with increased risk of lacunar infarcts in the deep white matter. CONCLUSIONS: The different risk factor profiles for new lacunar infarcts in basal ganglia and deep white matter indicate different etiologies. The independent association between progression of WMH and new deep white matter lacunar infarcts suggest a common etiology for these radiological abnormalities.

MRI of Cerebellar Infarction.

BACKGROUND: MRI is the imaging modality of choice for diagnosing brain infarction. Because of few or atypical clinical symptoms and a relatively low sensitivity of CT scans, many cerebellar infarctions may be detected only with MRI. With adequate recognition of cerebellar infarction on MRI and prompt initiation or optimisation of preventive therapeutic measures, more dramatic strokes may be avoided in selected cases. SUMMARY: We first briefly review the clinical presentation of cerebellar infarctions, followed by a short refresher on cerebellar anatomy and pathophysiological mechanisms of cerebellar infarcts. Then, we review the arterial cerebellar perfusion territories recently made visible with territorial arterial spin labeling (ASL), followed by a discussion and illustration of the MRI appearance of cerebellar infarcts in different stages. Similar to large cerebellar infarcts, recent studies investigating volumetric MRI datasets have now shown that small cerebellar infarcts occur in typical spatial patterns, knowledge of which may help in the diagnosis of even the smallest of cerebellar infarcts on MRI. Key Messages: MRI is the modality of choice for diagnosing cerebellar infarction. The posterior inferior cerebellar artery (PICA)-territories can be visualised with super-selective territorial ASL MRI. The PICA supplies at least the medial part of the posterior cerebellar surface. Anterior inferior cerebellar artery-infarcts can be mistaken for lateral PICA-infarcts. Small infarcts typically affect the cortex and often present as incidental cavities. Subacute cerebellar infarcts may be missed on imaging due to a phenomenon called "fogging."

Misinterpretation of ischaemic infarct location in relationship to the cerebrovascular territories.

PURPOSE: Cerebral perfusion territories are known to vary widely among individuals. This may lead to misinterpretation of the symptomatic artery in patients with ischaemic stroke to a wrong assumption of the underlying aetiology being thromboembolic or hypoperfusion. The aim of the present study was to investigate such potential misinterpretation with territorial arterial spin labelling (T-ASL) by correlating infarct location with imaging of the perfusion territory of the carotid arteries or basilar artery. MATERIALS AND METHODS: 223 patients with subacute stroke underwent MRI including structural imaging scans to determine infarct location, time-of-flight MR angiography (MRA) to determine the morphology of the circle of Willis and T-ASL to identify the perfusion territories of the internal carotid arteries, and basilar artery. Infarct location and the perfusion territory of its feeding artery were classified with standard MRI and MRA according to a perfusion atlas, and were compared to the classification made according to T-ASL. RESULTS: A total of 149 infarctions were detected in 87 of 223 patients. 15 out of 149 (10%) infarcts were erroneously attributed to a single perfusion territory; these infarcts were partly located in the originally determined perfusion territory but proved to be localised in the border zone with the adjacent perfusion territory instead. 12 out of 149 (8%) infarcts were misclassified with standard assessments and were not located in the original perfusion territory. CONCLUSIONS: T-ASL with territorial perfusion imaging may provide important additional information for classifying the symptomatic brain-feeding artery when compared to expert evaluation with MRI and MRA.

Cerebellar cortical infarct cavities and vertebral artery disease.

INTRODUCTION: Cerebellar cortical infarct cavities are a newly recognised entity associated with atherothromboembolic cerebrovascular disease and worse physical functioning. We aimed to investigate the relationship of cerebellar cortical infarct cavities with symptomatic vertebrobasilar ischaemia and with vascular risk factors. METHODS: We evaluated the MR images of 46 patients with a recent vertebrobasilar TIA or stroke and a symptomatic vertebral artery stenosis ≥50 % from the Vertebral Artery Stenting Trial (VAST) for the presence of cerebellar cortical infarct cavities ≤1.5 cm. At inclusion in VAST, data were obtained on age, sex, history of vertebrobasilar TIA or stroke, and vascular risk factors. Adjusted risk ratios were calculated with Poisson regression analyses for the relation between cerebellar cortical infarct cavities and vascular risk factors. RESULTS: Sixteen out of 46 (35 %) patients showed cerebellar cortical infarct cavities on the initial MRI, and only one of these 16 patients was known with a previous vertebrobasilar TIA or stroke. In patients with symptomatic vertebrobasilar ischaemia, risk factor profiles of patients with cerebellar cortical infarct cavities were not different from patients without these cavities. CONCLUSION: Cerebellar cortical infarct cavities are seen on MRI in as much as one third of patients with recently symptomatic vertebral artery stenosis. Since patients usually have no prior history of vertebrobasilar TIA or stroke, cerebellar cortical infarct cavities should be added to the spectrum of common incidental brain infarcts visible on routine MRI.

Selective Arterial Spin Labeling: Techniques and Neurovascular Applications.

Knowledge of the distribution of blood flowing from the heart to the brain-feeding arteries is important for the understanding and diagnosis of cerebrovascular diseases. Due to anatomical variations and anomalies within the cerebrovasculature, together with changes caused by various cerebrovascular diseases, there is high variability in the distribution of blood to the parenchyma. This article reviews the various methods that are available for determining the flow territories of the brain-feeding arteries and provides an overview of the different territorial arterial spin labeling (ASL) magnetic resonance imaging (MRI) techniques that have been introduced during the past 2 decades. ASL is a noninvasive method that uses arterial blood as an endogenous contrast agent by magnetically labeling the inflowing blood with radiofrequency pulses. Several selective ASL MRI methods are available to visualize the perfusion territories of individual brain feeding arteries and determine the presence of collateral blood flow pathways. Clinically, these selective perfusion methods may replace more invasive procedures such as catheter angiography for various diseases in which it is of importance to determine the feeding blood vessels, evaluate the presence potential collateral pathways, and monitor the patency of surgical bypasses.

Cerebellovascular Disease: Magnetic Resonance Imaging.

The goal of this thesis was to elucidate the details of cerebellovascular diseases with advanced magnetic resonance (MR) imaging (MRI) and to translate the findings to routine clinical MRI. The first aim was to image cerebellar arterial perfusion territories, which was achieved by applying super-selective arterial spin labelling (ASL) MRI with labelling of both vertebral arteries in addition to the carotid arteries. The second aim was to unravel the imaging patterns of cerebellar infarctions with 7T post-mortem MRI in addition to volume (3D) clinical MRI. This research led to the description of "cerebellar cortical infarct cavities", an incidental imaging finding that proved to be the most frequent manifestation of cerebellar ischemia as well as a marker of atherosclerotic and thromboembolic cerebrovascular disease. Finally, we found that almost all patients with such cavities lack a clinical history of vertebrobasilar transient ischemic attack (TIA) or stroke, disclosing the still very high incidence of clinically occult ischemia in the posterior fossa.

Cerebellar Cortical Infarct Cavities: Correlation With Risk Factors and MRI Markers of Cerebrovascular Disease.

BACKGROUND AND PURPOSE: Small cerebellar infarct cavities have been recently found on magnetic resonance imaging (MRI) to preferentially involve the cerebellar cortex, but epidemiological studies are lacking. We aimed to determine the prevalence and risk factor profiles of cerebellar cortical infarct cavities (≤1.5 cm) as well as their association with MRI markers of cerebrovascular disease and functioning. METHODS: We analyzed the 1.5 Tesla MRI of 636 patients (mean age, 62±9 years; 81% men) from the Second Manifestations of Arterial Disease-Memory, Depression and Aging (SMART-Medea) study. Logistic regression analyses were performed to estimate the associations of age, sex, vascular risk factors, MRI markers of cerebrovascular disease, and functioning with cerebellar cortical cavities, adjusted for age and sex. RESULTS: Cerebellar cortical infarct cavities occurred on MRI in 10% of patients and were significantly associated with age, intima-media thickness (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.7), high levels of homocysteinemia (OR, 1.8; 95% CI, 1.0-3.3), cortical infarcts (OR, 2.9; 95% CI, 1.6-5.4), gray matter lacunes of presumed vascular origin (OR, 3.0; 95% CI, 1.6-5.8), brain stem infarcts (OR, 5.1; 95% CI, 1.9-13.6), and decreased brain parenchymal fraction (OR, 0.84; 95% CI, 0.74-0.94), but not with white matter hyperintensities (OR, 1.2; 95% CI, 0.8-1.8) or white matter lacunes of presumed vascular origin (OR, 1.1; 95% CI, 0.5-2.5). They were also associated with worse physical functioning (OR, 0.96; 95% CI, 0.94 to -0.99) [corrected] but not with mental functioning. CONCLUSIONS: Cerebellar cortical infarct cavities are far more common than previously assumed based on symptomatic case series and are associated with markers of atherothromboembolic cerebrovascular disease.

Cerebellar infarct patterns: The SMART-Medea study.

OBJECTIVE: Previous studies on cerebellar infarcts have been largely restricted to acute infarcts in patients with clinical symptoms, and cerebellar infarcts have been evaluated with the almost exclusive use of transversal MR images. We aimed to document the occurrence and 3D-imaging patterns of cerebellar infarcts presenting as an incidental finding on MRI. METHODS: We analysed the 1.5 Tesla MRI, including 3D T1-weighted datasets, of 636 patients (mean age 62 ± 9 years, 81% male) from the SMART-Medea study. Cerebellar infarct analyses included an assessment of size, cavitation and gliosis, of grey and white matter involvement, and of infarct topography. RESULTS: One or more cerebellar infarcts (mean 1.97; range 1-11) were detected in 70 out of 636 patients (11%), with a total amount of 138 infarcts identified, 135 of which showed evidence of cavitation. The average mean axial diameter was 7 mm (range 2-54 mm), and 131 infarcts (95%) were smaller than 20 mm. Hundred-thirty-four infarcts (97%) involved the cortex, of which 12 in combination with subcortical white matter. No infarcts were restricted to subcortical branches of white matter. Small cortical infarcts involved the apex of a deep (pattern 1) or shallow fissure (pattern 2), or occurred alongside one (pattern 3) or opposite sides (pattern 4) of a fissure. Most (87%) cerebellar infarcts were situated in the posterior lobe. CONCLUSIONS: Small cerebellar infarcts proved to be much more common than larger infarcts, and preferentially involved the cortex. Small cortical infarcts predominantly involved the posterior lobes, showed sparing of subcortical white matter and occurred in characteristic topographic patterns.

High-resolution postcontrast time-of-flight MR angiography of intracranial perforators at 7.0 Tesla.

BACKGROUND AND PURPOSE: Different studies already demonstrated the benefits of 7T for precontrast TOF-MRA in the visualization of intracranial small vessels. The aim of this study was to assess the performance of high-resolution 7T TOF-MRA after the administration of a gadolinium-based contrast agent in visualizing intracranial perforating arteries. MATERIALS AND METHODS: Ten consecutive patients (7 male; mean age, 50.4 ± 9.9 years) who received TOF-MRA at 7T after contrast administration were retrospectively included in this study. Intracranial perforating arteries, branching from the parent arteries of the circle of Willis, were identified on all TOF-MRA images. Provided a TOF-MRA before contrast administration was present, a direct comparison between pre- and postcontrast TOF-MRA was made. RESULTS: It was possible to visualize intracranial perforating arteries branching off from the entire circle of Willis, and their proximal branches. The posterior cerebral artery (P1 and proximal segment of P2) appeared to have the largest number of visible perforating branches (mean of 5.1 in each patient, with a range of 2-7). The basilar artery and middle cerebral artery (M1 and proximal segment M2) followed with a mean number of 5.0 and 3.5 visible perforating branches (range of 1-9 and 1-8, respectively). Venous contamination in the postcontrast scans sometimes made it difficult to discern the arterial or venous nature of a vessel. CONCLUSION: High-resolution postcontrast TOF-MRA at 7T was able to visualize multiple intracranial perforators branching off from various parts of the circle of Willis and proximal intracranial arteries. Although confirmation in a larger study is needed, the administration of a contrast agent for high-resolution TOF-MRA at 7T seems to enable a better visualization of the distal segment of certain intracranial perforators.