Role of High-Resolution Dynamic Contrast-Enhanced MRI with Golden-Angle Radial Sparse Parallel Reconstruction to Identify the Normal Pituitary Gland in Patients with Macroadenomas.

BACKGROUND AND PURPOSE: Preoperative localization of the pituitary gland with imaging in patients with macroadenomas has been inadequately explored. The pituitary gland enhancing more avidly than a macroadenoma has been described in the literature. Taking advantage of this differential enhancement pattern, our aim was to evaluate the role of high-resolution dynamic MR imaging with golden-angle radial sparse parallel reconstruction in localizing the pituitary gland in patients undergoing trans-sphenoidal resection of a macroadenoma. MATERIALS AND METHODS: A retrospective study was performed in 17 patients who underwent trans-sphenoidal surgery for pituitary macroadenoma. Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were obtained. Using an ROI-based method to obtain signal-time curves and permeability measures, 3 separate readers identified the normal pituitary gland distinct from the macroadenoma. The readers' localizations were then compared with the intraoperative location of the gland. Statistical analyses were performed to assess the interobserver agreement and correlation with operative findings. RESULTS: The normal pituitary gland was found to have steeper enhancement-time curves as well as higher peak enhancement values compared with the macroadenoma (P < .001). Interobserver agreement was almost perfect in all 3 planes (κ = 0.89). In the 14 cases in which the gland was clearly identified intraoperatively, the correlation between the readers' localization and the true location derived from surgery was also nearly perfect (κ = 0.95). CONCLUSIONS: This study confirms our ability to consistently and accurately identify the normal pituitary gland in patients with macroadenomas with the golden-angle radial sparse parallel technique with quantitative permeability measurements and enhancement-time curves.

GPR133 (ADGRD1), an adhesion G-protein-coupled receptor, is necessary for glioblastoma growth.

Glioblastoma (GBM) is a deadly primary brain malignancy with extensive intratumoral hypoxia. Hypoxic regions of GBM contain stem-like cells and are associated with tumor growth and angiogenesis. The molecular mechanisms that regulate tumor growth in hypoxic conditions are incompletely understood. Here, we use primary human tumor biospecimens and cultures to identify GPR133 (ADGRD1), an orphan member of the adhesion family of G-protein-coupled receptors, as a critical regulator of the response to hypoxia and tumor growth in GBM. GPR133 is selectively expressed in CD133+ GBM stem cells (GSCs) and within the hypoxic areas of PPN in human biospecimens. GPR133 mRNA is transcriptionally upregulated by hypoxia in hypoxia-inducible factor 1α (Hif1α)-dependent manner. Genetic inhibition of GPR133 with short hairpin RNA reduces the prevalence of CD133+ GSCs, tumor cell proliferation and tumorsphere formation in vitro. Forskolin rescues the GPR133 knockdown phenotype, suggesting that GPR133 signaling is mediated by cAMP. Implantation of GBM cells with short hairpin RNA-mediated knockdown of GPR133 in the mouse brain markedly reduces tumor xenograft formation and increases host survival. Analysis of the TCGA data shows that GPR133 expression levels are inversely correlated with patient survival. These findings indicate that GPR133 is an important mediator of the hypoxic response in GBM and has significant protumorigenic functions. We propose that GPR133 represents a novel molecular target in GBM and possibly other malignancies where hypoxia is fundamental to pathogenesis.

Concurrent functional and metabolic assessment of brain tumors using hybrid PET/MR imaging.

To evaluate diagnostic accuracy of perfusion weighted imaging (PWI) and positron emission tomography (PET) using an integrated PET/MR system in tumor grading as well as in differentiating recurrent tumor from treatment-induced effects (TIE) in brain tumor patients. Twenty patients (Group A: treatment naïve, 9 patients with 16 lesions; Group B: post-therapy, 11 patients with 18 lesions) underwent fluorine 18 ((18)F) fluorodeoxyglucose (FDG) brain PET/MR with PWI. Two blinded readers predicted low versus high-grade tumor (for Group A) and tumor recurrence versus TIE (for Group B) based solely on tumor rCBV (regional cerebral blood volume) and SUV (standardized uptake values). Tumor histopathology at resection was the reference standard. Using rCBV(mean) ≤ 1.74 as a cut-off, 100% sensitivity and 74% specificity were observed, whereas 75% sensitivity and 89.7% specificity were observed with SUV(mean) ≤ 4.0 as a cut-off to classify patients as test positive for low-grade tumors (Group A) and TIE (Group B). Diagnostic accuracy for detection of low-grade tumors was 90% using PWI and 40% using PET in Group A (p = 0.056); for detection of TIE in Group B, diagnostic accuracy was 94.1% using PWI and 55.6% using PET (p = 0.033). No significant correlation was demonstrated between rCBV parameters and SUV in Group A (mean values: p > 0.403), Group B (p > 0.06) and in the entire population (p > 0.07). Best overall sensitivity and specificity were obtained using rCBV(mean) ≤ 1.74 and SUV(mean) ≤ 4.0 cut-off values. PWI demonstrated better diagnostic accuracy in both groups. Poor correlation was observed between FDG and rCBV parameters.

Glial neoplasms: dynamic contrast-enhanced T2*-weighted MR imaging.

PURPOSE: To evaluate the role of T2*-weighted echo-planar perfusion imaging by using a first-pass gadopentetate dimeglumine technique to determine the association of magnetic resonance (MR) imaging-derived cerebral blood volume (CBV) maps with histopathologic grading of astrocytomas and to improve the accuracy of targeting of stereotactic biopsy. MATERIALS AND METHODS: MR imaging was performed in 29 patients by using a first-pass gadopentetate dimeglumine T2*-weighted echo-planar perfusion sequence followed by conventional imaging. The perfusion data were processed to obtain a color map of relative regional CBV. This information formed the basis for targeting the stereotactic biopsy. Relative CBV values were computed with a nondiffusible tracer model. The relative CBV of lesions was expressed as a percentage of the relative CBV of normal white matter. The maximum relative CBV of each lesion was correlated with the histopathologic grading of astrocytomas obtained from samples from stereotactic biopsy or volumetric resection. RESULTS: The maximum relative CBV in high-grade astrocytomas (n = 26) varied from 1.73 to 13.7, with a mean of 5.07 +/- 2.79 (+/- SD), and in the low-grade cohort (n = 3) varied from 0.92 to 2.19, with a mean of 1.44 +/- 0.68. This difference in relative CBV was statistically significant (P < .001; Student t test). CONCLUSION: Echo-planar perfusion imaging is useful in the preoperative assessment of tumor grade and in providing diagnostic information not available with conventional MR imaging. The areas of perfusion abnormality are invaluable in the precise targeting of the stereotactic biopsy.

Mycosis fungoides metastasizing to the brain parenchyma: case report.

OBJECTIVE AND IMPORTANCE: Mycosis fungoides is a rare T-cell lymphoma of the skin that can, in one-half to three-quarters of patients suffering from this disease, involve the viscera in late stages of the disease. Although autopsy series performed more than 2 decades ago showed that the incidence of metastatic mycosis fungoides to the central nervous system is approximately one of seven, a total of only several dozen cases have been reported to date. As compared to meningeal involvement, intraparenchymal metastases are even rarer. We describe a biopsy-proven case of intraparenchymal central nervous system mycosis fungoides in a patient with nonprogressive skin involvement and no detectable visceral involvement, and we present a review of the relevant literature. CLINICAL PRESENTATION: A 68-year-old man, 3 years after the diagnosis of his skin disease, developed fatigue, confusion, and frontal lobe signs without the presence of cerebriform cells in the peripheral blood or any other clinical evidence of visceral involvement. Magnetic resonance imaging revealed a diffuse area of increased T2-weighted signal involving the white matter of both cerebral hemispheres as well as a focal area of T2 abnormality along the body of the corpus callosum. The radiological differential diagnosis was either leukodystrophy caused by chemotherapy, progressive multifocal leukoencephalopathy, or glioma with associated white matter changes. INTERVENTION: A stereotactic serial brain biopsy revealed diffuse perivascular infiltrates of atypical lymphocytes, as well as several large cells with cerebriform nuclei consistent with mycosis fungoides. The cells were immunoreactive for LCA, MT1, UCHL1, and CD3. CONCLUSION: We stress the importance of including mycosis fungoides as part of the differential diagnosis for a brain lesion in patients with cutaneous T-cell lymphoma, because treatments do exist, and we conclude that a serial stereotactic biopsy may be necessary to provide a definitive diagnosis.

Expression of a receptor protein tyrosine phosphatase in human glial tumors.

We have analyzed expression of a receptor protein tyrosine phosphatase (RPTPzeta/beta) in tissue samples from 23 human gliomas. Using the reverse transcription-polymerase chain reaction (RT-PCR) technique, we assayed for the presence or absence of mRNA transcripts encoding the intact receptor and 2 alternatively spliced forms of RPTPzeta/beta. Transcripts encoding the intact and truncated receptors were expressed in all of the lower grade gliomas (WHO grade 1-3) analyzed, but not in 55% of the grade 4 glioblastomas multiforme (GBM). However, this subset of GBMs did express an alternatively spliced secreted form comprised of only the RPTPzeta/beta extracellular domain. Our data suggests there may be a correlation between the loss of transcripts encoding the receptor forms of RPTPzeta/beta and progression from low to high grade gliomas. This work provides additional evidence for the importance of phosphatase isoform expression in human tumors.

Expression of the genes encoding myelin basic protein and proteolipid protein in human malignant gliomas.

Pathological differentiation of oligodendroglioma and mixed oligoastrocytoma from astrocytoma is difficult, relying on morphological characteristics due to the lack of reliable immunohistochemical stains. Oligodendrocytes, the presumed cell of origin of oligodendrogliomas, highly express the genes encoding myelin basic protein (MBP) and proteolipid protein (PLP). We analyzed the expression of these genes to determine whether they might be useful molecular markers of oligodendrocytic tumors. MBP and PLP were highly expressed in all oligodendrogliomas and minimally expressed in glioblastomas multiforme. MBP was highly expressed in mixed oligoastrocytomas, whereas PLP expression was minimal. The association between tumor classification and expression of the MBP and PLP genes was statistically significant. Expression of these genes may serve as a useful molecular marker for some subtypes of human gliomas.

The contralateral transcallosal approach: experience with 32 patients.

OBJECTIVE: To demonstrate the usefulness of the contralateral transcallosal approach for resecting lesions located laterally in or adjacent to the lateral ventricle. METHODS: Modifications to the standard ipsilateral transcallosal technique include positioning the head with the midline oriented horizontally, placing the side with the lesion up, and performing the craniotomy and interhemispheric dissection on the contralateral side. This approach avoids a transcortical incision, allows gravity to hold open the interhemispheric fissure, and increases the lateral exposure of the lesion. This approach was used in 32 patients with a variety of lesions, including 6 cavernous malformations, 7 arteriovenous malformations, and 19 tumors of various types. All but three lesions were located on the left side. RESULTS: All six cavernous malformations, all four benign tumors, and four of the seven arteriovenous malformations were resected completely. Malignant tumors were resected subtotally, and three arteriovenous malformations required stereotactic radiosurgery to treat residual deep nidus. There was no surgical mortality. Two patients experienced neurological deterioration. CONCLUSION: The contralateral transcallosal approach can be used to treat a variety of lesions safely and successfully.

Threaded steinmann pin fusion of the craniovertebral junction.

STUDY DESIGN: In a clinical retrospective study, the authors review long-term results of occipitocervical fusion using a wide diameter, contoured, threaded Steinmann pin. OBJECTIVES: To evaluate the clinical and radiographic results of occipitocervical fusion using this technique in a variety of abnormalities including rheumatoid arthritis. SUMMARY OF BACKGROUND DATA. The various surgical techniques and hardware developed for occipitocervical fusion have been associated with mixed results, particularly in patients with rheumatoid arthritis or basilar invagination. METHODS: Thirty-nine patients with occipitocervical instability were internally fixed with a wide diameter, contoured, threaded Steinmann pin wired to the occiput and cervical laminae or facets. Fusion was facilitated using autologous iliac crest bone graft and a cervical orthosis. Instability resulted from rheumatoid arthritis (n = 12), congenital anomalies (n = 12), trauma (n = 10), tumor (n = 4), or osteogenesis imperfecta (n = 1). Fifteen patients had radiographic evidence of basilar invagination. Long-term outcome (mean follow-up period, 38.9 months; range, 12-78 months) was based on clinical and radiographic review. RESULTS: Thirty-seven patients (97%) had a stable postoperative occipitocervical construct: there were 35 osseous unions, two fibrous unions, and one nonunion. There was on postoperative death from pulmonary complications. No patient developed evidence of new, recurrent, or progressive basilar invagination. CONCLUSION: The authors concluded that rigid segmental fixation of the craniovertebral junction using a wide diameter, contoured, threaded Steinmann pin and supplemental autograft creates excellent fusion with minimal complications. This technique is appropriate for a variety of abnormalities including rheumatoid arthritis.

Skull base tumors. A critical appraisal and clinical series employing image guidance.

Two of the most significant developments in neurosurgery over the past ten years have been the application of intraoperative navigational units and the widespread use of "skull base" surgical techniques. These developments have independently revolutionized the way in which neurosurgeons approach intracranial pathology. The combination of these two developments has had a profound effect in our clinical practice to improve outcome and extend our capabilities. This ability to see around the corner, "x-ray" vision as some have called it, provides an added measure of safety for the patient while allowing the surgeon to treat the lesion in a more aggressive fashion.

Clinical use of a frameless stereotactic arm: results of 325 cases.

The viewing wand is a frameless stereotactic arm that can be used in conjunction with computerized tomography (CT) or magnetic resonance (MR) imaging to provide image-based intraoperative navigation. The authors report a series of 325 cases in which the viewing wand was used and evaluated for its utility, ease of integration into the standard surgical setup, reliability, and real-world accuracy. The use of the system was associated with minimal additional effort or time spent in setting up the procedure as long as a trained technician performed the data transfer and reconstruction. The viewing wand was used in 165 cases in conjunction with CT and 145 cases with MR imaging. The system was reliable, achieving a useful registration in 310 of 325 cases (95.4%). Fiducial-based registration was more accurate than an anatomical landmark-surface fit algorithm method of registration (mean 2.8 vs. 5.6 mm error, respectively, for CT; and mean 3.0 vs. 6.2 mm for MR imaging). The actual error of the system in estimating the position of the probe tip just after registration was judged by the operating surgeon to be less than 2 mm in 92% of MR imaging cases and in 82% of CT cases, between 2 and 5 mm in 7% of MR imaging and 17% of CT cases, and greater than 5 mm in less than 1% of MR imaging and 1.2% of CT cases. The accuracy of the system degraded during the operation, so that by the third evaluation the error was estimated to be less than 2 mm in 77% of MR imaging and 62% of CT cases. Overall, the viewing wand was found to be reliable and accurate. This real-world accuracy was sufficient for a broad range of applications including glioma resection, cerebrospinal fluid shunting procedures, resection of small subcortical masses, and temporal lobe resection. The system is a useful navigational aid that allows a direct approach to intracranial pathology without the drawbacks of application and the limitations of a stereotactic frame.

Repair of vertebral artery injury during anterior cervical decompression.

METHODS: Vertebral artery injury is a rarely described complication of anterior cervical decompression. The authors performed a retrospective review of their operative database for the purposes of defining the optimal management of this complication and its avoidance. RESULTS: Four of 1,215 (0.3%) patients undergoing anterior cervical operation sustained arterial injuries. In three cases, primary repair of the artery was successful; in one case, the artery was exposed and ligated. There were no postoperative ischemic complications. Artery laceration occurred during decompression (n = 2), screw tapping (n = 1), and during soft tissue retraction (n = 1). CONCLUSIONS: Injury to the vertebral artery during anterior approaches can be avoided by preoperative identification of anomalous arteries and by intraoperative attention to the midline. When the artery is injured, primary repair may be the optimal management strategy.