Pathologic features of brain hemorrhage after radiation treatment: case series with somatic mutation analysis.

BACKGROUND: Radiation treatment for diseases of the brain can result in hemorrhagic adverse radiation effects. The underlying pathologic substrate of brain bleeding after irradiation has not been elucidated, nor potential associations with induced somatic mutations. METHODS: We retrospectively reviewed our department's pathology database over 5 years and identified 5 biopsy specimens (4 patients) for hemorrhagic lesions after brain irradiation. Tissues with active malignancy were excluded. Samples were characterized using H&E, Perl's Prussian Blue, and Masson's Trichrome; immunostaining for B-cells (anti-CD20), T-cells (anti-CD3), endothelium (anti-CD31), macrophages (anti-CD163), α-smooth muscle actin, and TUNEL. DNA analysis was done by two panels of next-generation sequencing for somatic mutations associated with known cerebrovascular anomalies. RESULTS: One lesion involved hemorrhagic expansion among multifocal microbleeds that had developed after craniospinal irradiation for distant medulloblastoma treatment. Three bleeds arose in the bed of focally irradiated arteriovenous malformations (AVM) after confirmed obliteration. A fifth specimen involved the radiation field distinct from an irradiated AVM bed. From these, 2 patterns of hemorrhagic vascular pathology were identified: encapsulated hematomas and cavernous-like malformations. All lesions included telangiectasias with dysmorphic endothelium, consistent with primordial cavernous malformations with an associated inflammatory response. DNA analysis demonstrated genetic variants in PIK3CA and/or PTEN genes but excluded mutations in CCM genes. CONCLUSIONS: Despite pathologic heterogeneity, brain bleeding after irradiation is uniformly associated with primordial cavernous-like telangiectasias and disruption of genes implicated in dysangiogenesis but not genes implicated as causative of cerebral cavernous malformations. This may implicate a novel signaling axis as an area for future study.

Temporal Changes on Postgadolinium MR Vessel Wall Imaging Captures Enhancement Kinetics of Intracranial Atherosclerotic Plaques and Aneurysms.

BACKGROUND AND PURPOSE: Analysis of vessel wall contrast kinetics (ie, wash-in/washout) is a promising method for the diagnosis and risk-stratification of intracranial atherosclerotic disease plaque (ICAD-P) and the intracranial aneurysm walls (IA-W). We used black-blood MR imaging or MR vessel wall imaging to evaluate the temporal relationship of gadolinium contrast uptake kinetics in ICAD-Ps and IA-Ws compared with normal anatomic reference structures. MATERIALS AND METHODS: Patients with ICAD-Ps or IAs who underwent MR vessel wall imaging with precontrast, early postcontrast (5-15 minutes), and delayed postcontrast (20-30 minutes) 3D T1-weighted TSE sequences were retrospectively studied. ROIs of a standardized diameter (2 mm) were used to measure the signal intensities of the cavernous sinus, pituitary infundibulum, temporalis muscle, and choroid plexus. Point ROIs were used for ICAD-Ps and IA-Ws. All ROI signal intensities were normalized to white matter signal intensity obtained using ROIs of 10-mm diameter. Measurements were acquired on precontrast, early postcontrast, and delayed postcontrast 3D T1 TSE sequences for each patient.ajnr;45/9/1206/T1T1T1Table 1:MR-VWI parameters for ICAD-Ps and IAsParameterValueSequence3D TSEScan planeAxialFOV (mm)160TR/TE (ms)800/28-32BW (Hx/pixel)370θ120Acceleration2ETL42Matrix acquisition0.5 mm ×0.5 mmMatrix recon0.5 mm ×0.5 mmNo. of slices/thick120/0.5Note:-FOV indicates field of view; TR, the repetition time; TE, the echo time; BW, bandwidth; ETL, echo train length; Matrix recon, matrix reconstruction. RESULTS: Ten patients with 17 symptomatic ICAD-Ps and 30 patients with 34 IA-Ws were included and demonstrated persisting contrast uptake (P < .001) of 7.21% and 10.54% beyond the early phase (5-15 minutes postcontrast) and in the delayed phase (20-30 minutes postcontrast) on postcontrast MR vessel wall imaging. However, normal anatomic reference structures including the pituitary infundibulum and cavernous sinus demonstrated a paradoxical contrast washout in the delayed phase. In both ICAD-Ps and IA-Ws, the greatest percentage of quantitative enhancement (>70%-90%) occurred in the early phase of postcontrast imaging, consistent with the rapid contrast uptake kinetics of neurovascular pathology. CONCLUSIONS: Using standard MR vessel wall imaging techniques, our results demonstrate the effects of gadolinium contrast uptake kinetics in ICAD-Ps and IA-Ws with extended accumulating enhancement into the delayed phase (> 15 minutes) as opposed to normal anatomic reference structures that conversely exhibit decreasing enhancement. Because these relative differences are used to assess qualitative patterns of ICAD-P and IA-W enhancement, our findings highlight the importance of standardizing acquisition time points and MR vessel wall imaging protocols to interpret pathologic enhancement for the risk stratification of cerebrovascular pathologies.