Value of coronal reformations in the CT evaluation of acute head trauma.

BACKGROUND AND PURPOSE: Routine axial CT images may not be ideally suited for detecting ICH in transversely oriented locations such as the floor of the anterior and middle cranial fossas and vertex. This study was performed to evaluate whether coronal reformations improve detection of ICH in NCCT performed for head trauma. MATERIALS AND METHODS: All patients undergoing a first NCCT in the ED for evaluation of head trauma were included prospectively during a 6-month interval. NCCT images were reconstructed into standard 5-mm axial datasets and were also reformatted into coronal datasets of 5-mm sections and 2.5-mm intervals. Thirty-two of 213 (15%) scans were interpreted as showing traumatic ICH. These cases were interspersed with 30 studies without ICH. Cases were reviewed for the presence and location of ICH by 2 staff neuroradiologists. RESULTS: Of 213 patients, 32 NCCTs demonstrated ICH (a total of 104 foci). Fifteen of 104 (14%) ICHs (8 patients) were detected solely on coronal images. Locations included the floor of the anterior and middle cranial fossas, vertex, corpus callosum, falx, tentorium, and occipital convexity. Coronal reformations allowed exclusion of suspicious findings on axial images in 14 instances (7 patients). Coronal images aided interpretation in 29/104 (28%) findings. CONCLUSIONS: Coronal reformations improve the detection of ICH over axial images alone, especially for lesions that lie in the axial plane immediately adjacent to bony surfaces. The use of coronal reformations should be considered in the routine interpretation of head CT examinations performed for the evaluation of head trauma.

Brain tumor imaging in clinical trials.

SUMMARY: There are substantial challenges in the radiologic evaluation of tumor size during clinical trials, and it is important for neuroradiologists to have a firm understanding of these issues. This review will examine measurement approaches, response criteria, selection of lesions for measurement, technical imaging considerations, interval between tumor measurements and response confirmation, and validity of imaging as a measure of efficacy.

Improved detection of skull metastasis with diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Metastasis to the skull is clinically important, but routine MR imaging offers moderate sensitivity for skull-metastasis detection in our experience. We sought to determine if diffusion-weighted MR imaging (DWI) could improve the detection of skull metastasis in patients with primary carcinomas that metastasized to bone compared with conventional MR imaging. MATERIALS AND METHODS: Seventy-five patients from the tumor registry of our institution with extracranial primary malignancy who had brain MR imaging with DWI and radionuclide bone scanning (RNBS, gold standard) within a 6-week interval were evaluated. Thirty-eight patients demonstrated increased radiopharmaceutical uptake on RNBS, consistent with skull metastasis of any size, and the remaining 37 were control subjects. Two readers correlated the DWI and conventional MR imaging with RNBS. RESULTS: The overall sensitivity of DWI for detection of skull metastases was 68.4%-71.1% (kappa=0.68) versus 42.1%-55.3% (kappa=0.65) for conventional MR imaging. Breast cancer (n=20) was detected with greatest sensitivity of 86.7%-93.3% (kappa=0.80) for DWI versus 60%-80% (kappa=0.5) for conventional MR imaging. Lung cancer (n=32) was detected with 63.6%-72.7% sensitivity (kappa=0.56), and prostate cancer (n=8) with 14.3% sensitivity (kappa=0.5) for DWI versus 27.3%-36.4% (kappa=0.81) and 14.3-42.9% (kappa=0), respectively, for conventional MR imaging. CONCLUSIONS: DWI is a useful sequence for identifying focal skull metastases for breast and lung malignancies and, compared with conventional MR imaging, provides improved detection of these lesions. DWI is insensitive for detecting skull metastases from prostate carcinoma.

Clinical and radiographic features of peritumoral infarction following resection of glioblastoma.

Focal areas of restricted diffusion adjacent to high-grade glioma resection cavities were detected in 70% of patients on immediate postoperative MRI studies. Follow-up studies demonstrated cystic encephalomalacia in 91% of these foci, suggesting the presence of infarction, and the infarcted tissue demonstrated enhancement in 43% of cases. New postoperative deficits correlated well with the anatomic region of infarction in six patients. Enhancement in perioperative infarcts can mimic tumor progression on follow-up imaging studies.

Improved detection of metastatic melanoma by T2*-weighted imaging.

BACKGROUND AND PURPOSE: The imaging features of metastatic melanomas are distinctive due to the presence of melanin and the propensity for hemorrhage. Both hemorrhage and melanin can produce T1-weighted hyperintensity and T2*-weighted signal intensity loss. We hypothesized that T2*-weighted images would improve detection of metastatic melanoma. METHODS: The T2* and T1 characteristics of 120 newly detected metastatic brain lesions from 31 patients with malignant melanoma were compared with those of 120 brain metastases from 23 patients with lung cancer. RESULTS: Melanoma metastases were 5 times more likely to demonstrate prominent T2*-related signal intensity loss (susceptibility effect) than were lung metastases (42% vs 8%; P < .01), and 4.5 times more likely to demonstrate T1 hyperintensity (55% vs 12%; P < .01). Patients with melanoma had lesions that were either hypointense on T2*-weighted images, hyperintense on T1 images, or both, in 71% (85/120), compared with 19% (23/120) of lung carcinoma metastases (P < .01). Melanoma lesions were 16 times more likely than lung cancer lesions to show combined T2* related signal intensity loss and T1 hyperintensity (P < .01). Remarkably, 8 melanoma lesions (7%) in 3 patients were detectable principally on the T2*-weighted sequences, whereas no lung cancer lesion was detected solely on susceptibility images. We found a direct correlation between melanin content and T1 hyperintensity but no correlation between T2* intensity and melanin. CONCLUSION: T2*-weighted images improve lesion detection in patients with melanoma metastases, and in conjunction with T1-weighted sequences, can suggest melanoma as the etiology of an intracranial mass. This sequence should be employed for evaluation of possible brain metastasis in patients without a known primary malignancy and in studies for melanoma staging.

Diagnostic evaluation of patients with a brain mass as the presenting manifestation of cancer.

BACKGROUND: Patients with a newly detected brain mass and no history of cancer often undergo extensive diagnostic testing in search of a systemic primary neoplasm prior to selection of a biopsy site, potentially leading to unnecessary expense and delay. We sought patterns in the evaluation of these patients to allow rapid selection of a biopsy site. METHODS: We compared the diagnostic evaluation of 176 patients with newly detected brain masses who were ultimately determined to have a metastatic or primary lesion. RESULTS: In 88 patients presenting with brain metastasis, lung cancer was markedly overrepresented as a primary tumor, occurring in 82% of patients. Brain MRI and chest CT together identified the site for diagnostic biopsy in all except for two of the 176 patients. One-half of the patients with metastasis had brain biopsy as the primary diagnostic procedure, with 80% undergoing a craniotomy rather than needle biopsy. The initial management decision in the majority of metastasis patients was whether to perform a craniotomy for resection of tumor. Whereas patients with single and cerebellar lesions were most likely to undergo craniotomy, the extent of systemic disease did not affect the decision to recommend a neurosurgical procedure. The average time to biopsy for patients with metastatic and primary tumors was 4.7 days and 6.0 days. In this retrospective population, we estimated that evaluation with brain MRI and chest CT, followed by an early neurosurgical decision, could reduce the time to diagnosis by at least 10%. CONCLUSIONS: Chest CT and brain MRI, if used together as initial diagnostic studies, would have identified a biopsy site in 97% of patients with a newly detected brain mass.

Molecular genetics of radiographically defined de novo glioblastoma multiforme.

Glioblastoma multiforme (GBM) represents the final endpoint of anaplastic progression in astrocytomas. GBM which arise without clinical evidence of a prior low-grade astrocytoma (LGA) have been designated de novo GBM, and are thought to develop rapidly from initial tumour formation. However, a purely clinical definition of de novo GBM does not exclude a long-standing, asymptomatic low-grade tumour. This study therefore sought to determine the genetic features of a unique group of cases in which GBMs were documented to have arisen radiographically in defined period of time (radiographically defined de novo GBM). Clinical and genetic features were examined in a group of 11 patients with a histological diagnosis of high-grade astrocytoma at first biopsy and radiographically defined de novo GBM. The mean age of the patients at tumour diagnosis was 62 years (range 32-87). Six of 11 tumours arose in the temporal lobes. Eight of 11 tumours had epidermal growth factor receptor (EGFR) overexpression, and EGFR gene amplification was found in five of the six analysed cases. Overexpression of p53 was observed in only one tumour, and a TP53 mutation was present in this case. p16 immunostaining was undetectable in 10 cases, and homozygous deletion of CDKN2A was observed in four of the six studied tumours. pRb expression was lost in four tumours. Mutations in the PTEN gene were detected in two of six cases. The results in this unique group of cases confirms the prior hypothesis that the profile of genetic alterations in de novo GBM is distinct from that of GBM arising from a known LGA, and that these specific genetic pathways promote the rapid development of GBM.

Spinal cord astrocytoma: response to PCV chemotherapy.

Information regarding the value of chemotherapy for spinal cord astrocytomas that progress after irradiation is limited. We describe a patient whose conus medullaris astrocytoma responded to PCV (procarbazine, lomustine, and vincristine) chemotherapy after failing radiation and cisplatin-based chemotherapy. PCV should be considered in patients with progressive spinal cord astrocytomas.

Glial cell-specific regulation of the JC virus early promoter by large T antigen.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease that results from an oligodendrocyte infection caused by JC virus. The JC virus early promoter directs cell-specific expression of the viral replication factor large T antigen, and thus transcriptional regulation constitutes a major mechanism of glial tropism in PML. We have previously demonstrated that T antigen controls the JC virus basal promoter in a glial cell-specific manner, since T antigen repressed the JC virus and simian virus 40 (SV40) early promoters in glioma cells but induced strong activation of the JC virus early promoter in nonglial cells. To further analyze these findings, T antigen and nuclear extracts from glial and nonglial cells were used to examine DNase I footprints on the proximal promoter. T-antigen binding to site II was more extensive than expected based on sequence homology with SV40, and nuclear proteins protected several regions of the proximal promoter in a cell-specific manner. Multiple Sp1 binding domains were identified. Site-directed mutagenesis revealed that T-antigen-mediated activation required a TATA box sequence, a pentanucleotide repeat immediately upstream of the TATA box, and an Sp1 binding site downstream of the TATA box. When footprints were obtained with mutant promoters which blocked T-antigen-induced transactivation, no change in T-antigen binding was observed. These results suggest that T antigen activates the JC virus basal promoter in nonglial cells by interaction with the transcription initiation complex.

Structural and functional brain asymmetries in human situs inversus totalis.

OBJECTIVE: To determine whether individuals with situs inversus totalis (SI), a condition in which there is a mirror-image reversal of asymmetric visceral organs, have alterations in brain asymmetries. BACKGROUND: The human brain is asymmetric in structure and function. Although correlations between anatomic asymmetries and functional lateralization in human brain have been demonstrated, it has been difficult to further analyze them. Characterization of asymmetries of brain structure and function in SI might advance the understanding of these relationships. METHODS: Using anatomic and functional MRI techniques, we analyzed asymmetries in the brains of three individuals with SI. RESULTS: Two major anatomic asymmetries of the cerebral hemispheres, the frontal and occipital petalia, were reversed in individuals with SI. In contrast, SI subjects had left cerebral hemisphere language dominance on functional MRI analysis as well as strong right-handedness. CONCLUSION: These observations suggest that the developmental factors determining anatomic asymmetry of the cerebral petalia and viscera are distinct from those producing the functional lateralization of language.

Cynomolgus polyoma virus infection: a new member of the polyoma virus family causes interstitial nephritis, ureteritis, and enteritis in immunosuppressed cynomolgus monkeys.

Polyoma virus infection causes acute interstitial nephritis and ureteral stenosis in humans but has rarely been noted in other species. In the present study, a hitherto unknown polyoma virus was detected in 12 of 57 cynomolgus monkeys after 3 to 11 weeks of immunosuppression given to promote acceptance of renal allografts or xenografts. This virus, termed cynomolgus polyoma virus (CPV), is antigenically and genomically related to simian virus 40 (SV40). The tubular epithelial nuclei of the collecting ducts in the medulla and cortex reacted with an antibody for the SV40 large T antigen and by electron microscopy contained densely packed paracrystalline arrays of 30- to 32-nm diameter viral particles. A polymerase chain reaction analysis of DNA extracted from affected kidneys detected polyoma virus sequences using primers for a highly conserved region of the large T antigen of polyoma virus. Sequence analysis showed 7 base substitutions and 3 to 5 deletions in the 129-nucleotide segment of amplified products, compared with the corresponding portion of SV40, yielding 84% homology at the amino acid level. CPV caused interstitial nephritis in six renal allografts, a xenograft kidney, and six native kidneys. Infected animals showed renal dysfunction and had tubulointerstitial nephritis with nuclear inclusions, apoptosis, and progressive destruction of collecting ducts. CPV was detected in the urothelium of graft ureters, associated with ureteritis and renal infection. Viral infection was demonstrable in smooth muscle cells of the ureteric wall, which showed apoptosis. One animal had diarrhea and polyoma virus infection in the smooth muscle cells of the muscularis propria of the intestine. Spontaneous resolution occurred in one case; no animal had virus detected in tissues more than 3 months after transplantation. Thus, immunosuppression predisposes cynomolgus monkeys to a polyoma virus infection with clinical consequences quite similar to BK virus infection in humans, including renal dysfunction. We also suggest that this may be the pathogenetic basis for the significant incidence of late onset, isolated ureteral stenosis observed in these recipients.

Age-dependent rate of anaplastic transformation in low-grade astrocytoma.

Age and histologic grade are interrelated characteristics of diffuse fibrillary astrocytomas, because the peak age incidence rises with increasing grade. The relationship between age and grade may be explained if age determines the rate of anaplastic progression in astrocytomas. The authors tested this hypothesis by determining the interval between diagnosis of low-grade astrocytoma and progression to high-grade astrocytoma in patients of various ages. A two-way scatterplot of age at initial diagnosis versus interval to anaplastic progression demonstrated a strong negative correlation (n = 24; Pearson correlation coefficient = -0.83; Spearman correlation coefficient = -0.79; p < 0.001 for both values). It was concluded that the rate of anaplastic progression in low-grade astrocytoma is directly correlated with patient age.

Radiation-associated cerebral blindness.

PURPOSE: To report a case of blindness caused by a white-matter injury after whole brain irradiation for metastatic renal cell carcinoma. METHODS: Case report. We performed comprehensive serial neuro-ophthalmologic examinations. RESULTS: Four to 5 months after resection of renal cell metastasis in the left occipital cortex, interleukin-2 therapy, and whole brain irradiation with 3,000 cGy plus a 1,500-cGy boost to the posterior third of the brain, the patient developed a progressive decline in visual acuity in both eyes to hand motions. Magnetic resonance imaging disclosed signal abnormalities without mass effect in the white matter of the parietal and occipital lobes bilaterally, including the optic radiations. CONCLUSION: This case is a unique example of cortical blindness secondary to radiation injury in the occipital lobes and optic radiations.

Spinal dural enhancement on magnetic resonance imaging associated with spontaneous intracranial hypotension. Report of three cases and review of the literature.

This report offers a description of typical changes seen on gadolinium-enhanced magnetic resonance (MR) imaging of the entire spine that indicate spontaneous intracranial hypotension (SIH). To the authors' knowledge, this is the first report of its kind. They describe three cases of SIH that were accompanied by dural enhancement throughout the neuraxis on imaging, with the evolution of associated subdural and epidural fluid collections in the spine. Recognition of this disorder is important to be able to distinguish it from an infectious or neoplastic process in which surgical intervention might be warranted. Evaluation using gadolinium-enhanced cranial and spinal MR imaging in patients with postural headaches and an (111)In-labeled cerebrospinal fluid leak study are discussed. Treatment with an epidural blood patch is shown to be particularly effective, with resolution of the radiological and clinical findings.