Ana M. Franceschi

T2-FLAIR Mismatch, an Imaging Biomarker for IDH and 1p/19q Status in Lower Grade Gliomas: A TCGA/TCIA Project

Purpose: Lower-grade gliomas (WHO grade II/III) have been classified into clinically relevant molecular subtypes based on IDH and 1p/19q mutation status. The purpose was to investigate whether T2/FLAIR MRI features could distinguish between lower-grade glioma molecular subtypes. Experimental Design: MRI scans from the TCGA/TCIA lower grade glioma database (n = 125) were evaluated by two independent neuroradiologists to assess (i) presence/absence of homogenous signal on T2WI; (ii) presence/absence of “T2–FLAIR mismatch” sign; (iii) sharp or indistinct lesion margins; and (iv) presence/absence of peritumoral edema. Metrics with moderate–substantial agreement underwent consensus review and were correlated with glioma molecular subtypes. Somatic mutation, DNA copy number, DNA methylation, gene expression, and protein array data from the TCGA lower-grade glioma database were analyzed for molecular–radiographic associations. A separate institutional cohort (n = 82) was analyzed to validate the T2–FLAIR mismatch sign. Results: Among TCGA/TCIA cases, interreader agreement was calculated for lesion homogeneity [κ = 0.234 (0.111–0.358)], T2–FLAIR mismatch sign [κ = 0.728 (0.538–0.918)], lesion margins [κ = 0.292 (0.135–0.449)], and peritumoral edema [κ = 0.173 (0.096–0.250)]. All 15 cases that were positive for the T2–FLAIR mismatch sign were IDH-mutant, 1p/19q non-codeleted tumors (P < 0.0001; PPV = 100%, NPV = 54%). Analysis of the validation cohort demonstrated substantial interreader agreement for the T2–FLAIR mismatch sign [κ = 0.747 (0.536–0.958)]; all 10 cases positive for the T2–FLAIR mismatch sign were IDH-mutant, 1p/19q non-codeleted tumors (P < 0.00001; PPV = 100%, NPV = 76%). Conclusions: Among lower-grade gliomas, T2–FLAIR mismatch sign represents a highly specific imaging biomarker for the IDH-mutant, 1p/19q non-codeleted molecular subtype. Clin Cancer Res; 23(20); 6078–85. ©2017 AACR.

Use of Susceptibility-Weighted Imaging (SWI) in the Detection of Brain Hemorrhagic Metastases from Breast Cancer and Melanoma

Purpose Susceptibility-weighted imaging (SWI) has significantly increased our sensitivity in detecting hemorrhagic brain lesions. We sought to explore the prevalence of intratumoral hemorrhage as detected by SWI in brain metastases from melanoma and breast cancer. Methods Lesions with a size of 0.1 cm3 were categorized as micrometastases, whereas larger lesions were categorized as macrometastases. Susceptibility-weighted imaging findings on locations corresponding to enhancing lesions were categorized as either positive or negative based on presence/absence of signal dropout. The percentage of SWI positivity was then estimated as a function of lesion size. Two-tailed Fisher exact test was performed to examine differences in the contingency tables. Results Magnetic resonance imaging studies from 73 patients with 1173 brain metastases, which enhanced on postcontrast T1-weighted imaging (T1WI) were selected for analysis. Of these lesions, 952 had SWI data available, and 342 of 952 were micrometastases. Only 10 of the 342 micrometastases and 410 (67.2%) of the 610 macrometastases were SWI positive (P < 0.0001). When examined by tumor type, 76.9% (melanoma) versus 55.6% (breast cancer) were SWI positive (P < 0.0001), regardless of tumor size. All melanoma lesions (8/8) and only 1 of 15 breast cancer lesions larger than 1.5 cm3 were SWI positive. Conclusion With the use of combined SWI and contrast-enhanced high-resolution T1 imaging, we found that presence of intratumoral brain hemorrhage is uncommon in micrometastases but common in metastases greater than 0.1 cm3 from breast cancer or melanoma. Large metastases commonly harbored hemorrhage, and this occurred more frequently in patients with melanoma than with breast cancer.

Posterior Cortical Atrophy

Posterior cortical atrophy is a progressive neurodegenerative disorder that predominantly affects the occipital cortex and is referred to as a “visual variant of Alzheimer’s disease.” PET/MR imaging demonstrates hypometabolism in the parieto-occipital areas with relative sparing of the cingulate gyrus as well as in the bilateral frontal eye field regions. Cortical volume loss is seen later in the disease course.

Mesial Temporal Lobe Sclerosis

Mesial temporal sclerosis is the most common cause of temporal lobe epilepsy. The combination of anatomic and functional information with PET/MR imaging precisely localizes the seizure focus.

Recurrent Prostate Cancer with Fluciclovine

Fluciclovine is a radiotracer indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate-specific antigen levels treated by hormone therapy or castrate-resistant prostate cancer. Fluciclovine is effective as part of a whole-body PET/MR imaging protocol and aids in the detection of local, lymph node, and bone relapse of metastatic prostate cancer.

Amyloid Plaques in Alzheimer’s Disease

Florbetapir is a radiotracer used to evaluate the amyloid plaque burden in patients with clinical suspicion for Alzheimer’s disease. When a patient undergoes amyloid plaque imaging using PET/MR scan for evaluation of suspected AD, the structural assessment provided by MR complements the PET interpretation.

Dementia with Lewy Body

Dementia with Lewy body (DLB) is characterized by cognitive decline, visual hallucinations, and motor Parkinsonism. Hybrid PET/MR imaging is useful in differentiating DLB from other neurodegenerative disorders as there is less pronounced global atrophy and hypometabolism that also affects the occipital lobes in addition to the posterior temporal and parietal lobes.

Crossed Cerebellar Diaschisis

Crossed cerebellar diaschisis is characterized by depressed blood flow, decreased metabolism, and resulting atrophy of a cerebellar hemisphere caused by injury or lesion involving the contralateral supratentorial cerebral hemisphere. PET/MR imaging provides the anatomical detail to identify the cerebral insult and demonstrates depressed metabolism in the contralateral cerebellar hemisphere.

Recurrent Salivary Gland Cancer

Adenoid cystic carcinoma, which typically involves the minor salivary glands, demonstrates intermediate signal intensity on T1-weighted images, but is hyperintense on T2-weighted sequences with marked, homogeneous contrast enhancement and increased uptake on FDG PET/MR imaging.

Creutzfeldt-Jakob Disease

Creutzfeldt-Jakob disease is a type of spongiform encephalopathy caused by an infectious protein agent called a prion. PET/MR imaging shows T2 and FLAIR hyperintensity in the basal ganglia and cerebral cortex with decreased FDG uptake.