Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma

Meningiomas are the most common primary intracranial tumors, but the molecular drivers of meningioma tumorigenesis are poorly understood. We hypothesized that investigating intratumor heterogeneity in meningiomas would elucidate biologic drivers and reveal new targets for molecular therapy. To test this hypothesis, here we perform multiplatform molecular profiling of 86 spatially-distinct samples from 13 human meningiomas. Our data reveal that regional alterations in chromosome structure underlie clonal transcriptomic, epigenomic, and histopathologic signatures in meningioma. Stereotactic co-registration of sample coordinates to preoperative magnetic resonance images further suggest that high apparent diffusion coefficient (ADC) distinguishes meningioma regions with proliferating cells enriched for developmental gene expression programs. To understand the function of these genes in meningioma, we develop a human cerebral organoid model of meningioma and validate the high ADC marker genes CDH2 and PTPRZ1 as potential targets for meningioma therapy using live imaging, single cell RNA sequencing, CRISPR interference, and pharmacology.

Magnetic Resonance Imaging of Uncommon Hepatic Mesenchymal Tumours: Haemangioendothelioma and Angiosarcoma

<P>Background: Primary Hepatic Epithelioid Haemangioendothelioma (HEHE) and Primary Hepatic Angiosarcoma (PHA) are rare mesenchymal tumours with different malignant potential. Whereas HEHE demonstrates low to intermediate malignant potential, PHA is an aggressive malignancy with poor prognosis. The knowledge of typical imaging features of these lesions may facilitate correct diagnosis; however, the ultimate diagnosis of HEHE and PHA is based on histopathologic examination. </P><P> Discussion: The most typical findings helpful in diagnosing HEHE are: Presence of multiple, confluent nodules located at the liver periphery (in young to middle-aged woman), retraction of the liver capsule, marked hyperintensity on T2-weighted images, “target-sign” appearance, progressive centripetal contrast enhancement, and relatively high Apparent Diffusion Coefficient (ADC) values. More than &#8805;50% of nodules are hyper- or isointense on Hepatobiliary Phase (HBP) images. Conclusion: The imaging features suggestive of PHA are: Occurrence of metastases (lungs, spleen) at the time of diagnosis, presence of a large dominant mass with smaller satellites, heterogeneity and areas of haemorrhage in a dominant mass, progressive contrast enhancement, slightly elevated ADC values as compared to other malignant liver tumours.</P>

Intracranial dural chondroma in a child—conventional and advanced neuroimaging characteristics and differential diagnosis

Intracranial chondromas are rare tumors, especially in the pediatric population. We describe the conventional and advanced neuroimaging characteristics of this rare convexity dura-based chondroma in a young adolescent. In particular we demonstrate that diffusion-weighted imaging (DWI) facilitates differentiation between a dura-based chondroma and the more frequent classical meningioma. Chondromas are typically DWI hypointense with high apparent diffusion coefficient (ADC) values while meningiomas are typically DWI hyperintense with low ADC values. We also discuss the relevant additional differential diagnoses of dura based focal lesions for the pediatric population as well as the diagnostic significance of additional imaging modalities, including computed tomography, magnetic resonance imaging and cerebral angiography.

Brain Magnetic Resonance Spectroscopy in Episodic Hepatic Encephalopathy

Brain magnetic resonance (MR) study has shown metabolic abnormalities and changes in water distribution of the brain tissue that may relate to the pathogenesis of hepatic encephalopathy (HE). We designed a study to investigate the disturbances in brain water and metabolites during episodic HE using a 3-T MR scanner. Cirrhotic patients with different grades of HE underwent MR during hospitalization ( n = 18). The MR was repeated at 6 weeks' follow-up ( n = 14). The results were compared with those of a group of healthy volunteers ( n = 8). During episodic HE, brain diffusion-weighted imaging showed a high apparent diffusion coefficient (ADC) (12% to 14%) that decreased during follow-up (–1% to −4%). These disturbances were accompanied by high glutamine (581%), low choline (–31%), and low myo-inositol (–86%) peaks on MR spectroscopy. In overt HE, patients showed high glutamine that decreased during follow-up (–22%). In addition, these patients exhibited a rise in plasma S100 beta and enlargement of brain white-matter lesions. In conclusion, several disturbances detected by MR support the presence of impaired brain water homeostasis during episodic HE. Although astrocytes have a major role in this condition, brain edema during episodic HE may be extracellular and does not appear to be directly responsible for the development of neurologic manifestations.

Hypertensive brainstem encephalopathy involving deep supratentorial regions: does only blood pressure matter?

We report on a 42-year-old female patient who presented with high arterial blood pressure of 245/150 mmHg and hypertensive brainstem encephalopathy that involved the brainstem and extensive supratentorial deep gray and white matter. The lesions were nearly completely resolved several days after stabilization of the arterial blood pressure. Normal diffusion-weighted imaging findings and high apparent diffusion coefficient values suggested that the main pathomechanism was vasogenic edema owing to severe hypertension. On the basis of a literature review, the absolute value of blood pressure or whether the patient can control his/her blood pressure seems not to be associated with the degree of the lesions evident on magnetic resonance imaging. It remains to be determined if the acceleration rate and the duration of elevated arterial blood pressure might play a key role in the development of the hypertensive encephalopathy pattern.