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.

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.

Gamma knife radiosurgery for multiple sclerosis-related trigeminal neuralgia.

BACKGROUND: Surgical options for multiple sclerosis (MS) related to trigeminal neuralgia (TN), a severe and disabling pain disorder, include percutaneous rhizotomy, stereotactic radiosurgery, or microsurgical nerve section. Our goal was to evaluate clinical outcomes after gamma knife radiosurgery (GKRS) in patients with MS with TN. METHODS: We evaluated clinical outcomes in 37 patients with TN managed over a 12-year period. The maximum TN target dose varied between 70 and 90 Gy. Seventy-eight percent of patients had failed prior surgery. In 9, GKRS was the first procedure. Median follow-up was 56.7 months (range, 6-174). Pain relief was assessed in each patient by physicians who did not participate in the surgery. RESULTS: Eventual complete pain relief (BNI grade I) after GKRS and reasonable pain control (BNI grade I-IIIb) after GKRS were noted in 23 patients (62.1%) and 36 patients (97.3%) at some point in their course. Reasonable pain control (BNI grade I-IIIb) after GKRS was maintained in 82.6%, 73.9%, and 54.0% of patients after 1, 3, and 5 years. Fourteen patients (37.8%) underwent a second or a subsequent procedure for residual or recurrent pain. Eight patients underwent a second GKRS, 5 underwent percutaneous glycerol rhizotomy, and 1 underwent balloon microcompression. The complication rate after GKRS was 5.4% (new onset of nondisabling paresthesias). No patient developed dysesthesias. CONCLUSIONS: Gamma knife radiosurgery is the most minimally invasive surgical technique for multiple sclerosis-related trigeminal neuralgia and has low morbidity. For this reason, gamma knife radiosurgery proved to be a satisfactory management strategy for multiple sclerosis-related trigeminal neuralgia.

Recursive partitioning analysis of prognostic factors for patients with four or more intracranial metastases treated with radiosurgery.

The purpose of this study was to devise a new recursive partitioning analysis (RPA) of patients with four or more intracranial metastases treated with a single radiosurgery procedure to identify a class of patients with extended survival. 205 patients underwent Gamma Knife radiosurgery for four or more intracranial metastases (median = 5, range 4-18) during one session. The median total treatment volume was 6.8 cc (range 0.6-51.0 cc). Radiosurgery was used as sole management (17% of patients), or in combination with WB-RT (46%), or after failure of WB-RT (38%). The median marginal radiosurgery dose was 16 Gy (range 12-20 Gy). RPA assessed the effects of age, Karnofsky >70, extracranial disease, visceral metastases, number of metastases, total treatment volume, history of breast and melanoma primaries on survival. The median overall survival after radiosurgery for all patients was 8 months. RPA identified a favorable subgroup of 78 patients (43% of the series) with a total treatment volume <7 cc and < 7 brain metastases (Class 1), with a median survival of 13 months. This subgroup's survival was significantly better (p <0.00005) than the remaining patients (Class 2) (n=111) with a median survival of 6 months. In conclusion, RPA of multiple brain metastasis patients identified 2 distinct cohorts of patients. Class 1 patients have a total treatment volume <7 cc and < 7 metastases (4-6) with favorable survival after Radiosurgery and Class 2 patients have a total treatment volume > or = 7 cc and/or > or = 7 metastases and have a significantly poorer survival.

Toward effective needle steering in brain tissue.

Recent research has exploited the inherent bending of a bevel-tipped needle during insertion, accomplishing steering of the needle by rotating the needle shaft. Combining this technique with the observation that a straight trajectory can be accomplished by spinning the needle at a constant rate during insertion, this paper presents a novel technique for proportional control of the curvature of the trajectory via duty-cycled spinning of the needle. In order to accommodate this technique to very soft tissues such as the brain, several custom needle prototypes have also been designed in order to increase the steering versatility of the system by maximizing the attainable curvature. The paper describes the needle-steering system and the needle prototypes, and presents preliminary results from tests in an artificial brain tissue substitute.

Sensitivity to radiation-induced apoptosis and neuron loss declines rapidly in the postnatal mouse neocortex.

Therapeutic brain irradiation can cause progressive decline in cognitive function, particularly in children, but the reason for this effect is unclear. The study explored whether age-related differences in apoptotic sensitivity might contribute to the increased vulnerability of the young brain to radiation. Postnatal day 1 (P1) to P30 mice were treated with 0-16 Gy whole-body X-irradiation. Apoptotic cells were identified and quantified up to 48 h later using the TdT-UTP nick end-labelling method (TUNEL) and immunohistochemistry for activated caspase-3. The number of neuron-specific nuclear protein (NeuN)-positive and -negative cells were also counted to measure neuronal and non-neuronal cell loss. Significantly greater TUNEL labelling occurred in the cortex of irradiated P1 animals relative to the other age groups, but there was no difference among the P7, P14 and P30 groups. Irradiation decreased the %NeuN-positive cells in the mice irradiated on P1, whereas in P14 animals, irradiation led to an increase in the %NeuN-positive cells. These data demonstrate that neocortical neurons of very young mice are more susceptible to radiation-induced apoptosis. However, this sensitivity decreases rapidly after birth. By P14, acute cell loss due to radiation occurs primarily in non-neuronal populations.

Changes in cognitive function after neuronal cell transplantation for basal ganglia stroke.

Reported is the change in cognitive function after neuronal cell transplantation as a treatment for basal ganglia stroke. Nine subjects (two controls, seven transplants), all over 2 years post stroke, completed a comprehensive neuropsychological test battery prior to and 6 months after treatment. Four transplanted subjects who had strokes in the nondominant hemisphere showed marked improvement on the Rey Complex Figure, a test of visuospatial/constructional ability and nonverbal memory.

Safety and biodistribution studies of an HSV multigene vector following intracranial delivery to non-human primates.

Malignant glioma is a fatal human cancer in which surgery, chemo- and radiation therapies are ineffective. Therapeutic gene transfer used in combination with current treatment methods may augment their effectiveness with improved clinical outcome. We have shown that NUREL-C2, a replication-defective multigene HSV-based vector, is effective in treating animal models of glioma. Here, we report safety and biodistribution studies of NUREL-C2 using rhesus macaques as a model host. Increasing total doses (1 x 10(7) to 1 x 10(9) plaque forming units (PFU)) of NUREL-C2 were delivered into the cortex with concomitant delivery of ganciclovir (GCV). The animals were evaluated for changes in behavior, alterations in blood cell counts and chemistry. The results showed that animal behavior was generally unchanged, although the chronic intermediate dose animal became slightly ataxic on day 12 postinjection, a condition resolved by treatment with aspirin. The blood chemistries were unremarkable for all doses. At 4 days following vector injections, magnetic resonance imaging showed inflammatory changes at sites of vector injections concomitant with HSV-TK and TNFalpha expression. The inflammatory response was reduced at 14 days, resolving by 1 month postinjection, a time point when transgene expression also became undetectable. Immunohistochemical staining following animal killing showed the presence of a diffuse low-grade gliosis with infiltrating macrophages localized to the injection site, which also resolved by 1 month postinoculation. Viral antigens were not detected and injected animals did not develop HSV-neutralizing antibodies. Biodistribution studies revealed that vector genomes remained at the site of injection and were not detected in other tissues including contralateral brain. We concluded that intracranial delivery of 1 x 10(9) PFU NUREL-C2, the highest anticipated patient dose, was well tolerated and should be suitable for safety testing in humans.

Fractionation of radiation treatment in acoustics. Rationale and evidence in comparison to radiosurgery.

Stereotactic fractionated radiotherapy has been proposed as a strategy to improve upon the results of single-fraction radiosurgery. The rationale for the strategy is that fractionation will allow complciations to be reduced while maintaining the same degree of long-term tumor control. This paper reviews the radiobiological arguements for fractionating radiation treatment of acoustic neuromas and examines claims for improvement in outcome.

Acoustic neuroma radiosurgery. Origins, contemporary use and future expectations.

Patients who have an acoustic neuroma (vestibular schwannoma) can be managed with observation, open surgical resection, stereotactic radiosurgery, or fractionated radiotherapy. Increasing numbers of patients are choosing radiosurgery over resection for their tumor. In this report we discuss the history of stereotactic radiosurgery, and the evolution in technique that has led to current results with this approach. We discuss the indications for and expectations with the different treatments. The literature on radiosurgery and radiotherapy is reviewed. It is expected that clinical and basic studies will further improve results.

Non-invasive assessment of tumor proliferation using triple quantum filtered 23/Na MRI: technical challenges and solutions.

We address the development of triple-quantum-filtered sodium MRI as a non-invasive surrogate measure for cell proliferation in brain tumors. We demonstrate that through careful consideration of the theoretical description of the signal, triple-quantum-filtered sodium images of adequate signal-to-noise ratio (SNR) can be acquired in clinically acceptable imaging times.

Controversies in the management of multiple brain metastases: the roles of radiosurgery and radiation therapy.

Multiple brain metastases (BrM) are a common challenge to patients with cancer. Tumour resection is used mainly for patients with large tumours that cause acute neurological syndromes. The prognosis, even after treatment with whole brain radiation therapy (WBRT), is poor with average expected survivals less than six months. For this reason, numerous centres have evaluated the role of stereotactic radiosurgery (SRS) in patients with solitary or multiple tumours. We conducted a randomised trial that compared radiosurgery plus WBRT to WBRT alone. The rate of local failure at one year was 100% after WBRT alone but only 8% in patients who had boost radiosurgery. The median time to local failure was six months after WBRT alone in comparison to 36 months after WBRT plus radiosurgery (p=0.0005). The median time to any brain failure was improved in the radiosurgery group (p=0.002). Survival was related to extent of extracranial disease (p=0.02). Combined WBRT and radiosurgery for patients with two to four BrM significantly improves control of brain disease. WBRT alone, for years the standard treatment, does not appear to provide lasting and effective care for most patients. Controversies remain in patient selection, number of BrM suitable for treatment, concomitant management of extracranial disease, and timing of therapy.

Stereotactic radiosurgery for residual neurocytoma. Report of four cases.

The purpose of this report was to review the results of stereotactic radiosurgery in the management of patients with residual neurocytomas after initial resection or biopsy procedures. Four patients underwent stereotactic radiosurgery for histologically proven neurocytoma. Clinical and imaging studies were performed to evaluate the response to treatment. Radiosurgery was performed to deliver doses to the tumor margin of 14, 15, 16, and 20 Gy, depending on tumor volume and proximity to critical adjacent structures. More than 3 years later, imaging studies revealed significant reductions in tumor size. No new neurological deficits were identified at 53, 50, 42, and 38 months of follow up. The authors' initial experience shows that stereotactic radiosurgery appears to be an effective treatment for neurocytoma.

[Radiosurgery of the brain at the beginning of the 21st century: gamma knife with C-table]. / Sugár agysebészet a XXI. Század hajnalán: a gamma-kés C-modell automata pozícionáló robot rendszerrel.

The goal of stereotactic radiosurgery by definition is "the delivery of a single, high dose of radiation allowing the precise and complete destruction of chosen target structures containing healthy and/or pathological cells, without significant concomitant or late radiation damage to adjacent tissues". This effect is obtained by the precise focusing of multiple low energy radiation beams crossing at the target. Three different techniques can be used for radiosurgery: linear accelerator (LINAC) based radiosurgery, Bragg-peak (proton) therapy and Gamma Knife radiosurgery. Leksell Gamma Knife (LGK) is a dedicated neurosurgical device for brain surgery to destroy predetermined intracranial targets through the intact skull. It operates via the radiobiological effect of stereotactically directed, highly focused ionizing gamma-beams of 201 cobalt-60 sources. The LGK offers the best precision of target during irradiation. The mechanical accuracy is about 0.3 mm, which makes it particularly suitable for highly sophisticated neurosurgical interventions. Radiosurgery was originally developed to treat functional neurological disorders, but soon after its introduction cerebral arteriovenous malformations, and brain tumors became the main targets for the technique. Since the first LGK installation at the Sophiahemmet Hospital, Stockholm, Sweden in 1967, over 150,000 patients have already been treated in more than 150 units worldwide. The accumulated clinical experience with the LGK has established this method as the "golden standard" of radiosurgery. In December 1999, a new development, the LGK Model-C was installed at the Centre Gamma Knife, Université Libre de Bruxelles, Hôpital Académique Erasme, Brussels, Belgium. This was followed by completion of two similar units in Krefeld, Germany, and at the Presbyterian University Hospital, Pittsburgh, Pennsylvania, U.S.A. The major innovation in the design of the LGK Model-C is the robotic Automatic Positioning System, which allows computer-controlled automatic and sequential positioning of multiple shots during treatment. Thus all steps of the procedure are performed through an unbroken digital chain, from stereotactic image acquisition to the control of the irradiation sequence. This represents a significant achievement which increases the accuracy and practicality of the treatment. The technical details of the method are described, and the main treatment indications are reviewed.

An analysis of the effects of smoking and other cardiovascular risk factors on obliteration rates after arteriovenous malformation radiosurgery.

PURPOSE: To assess the relationships of smoking and other cardiovascular disease risk factors (hypertension, diabetes, hypercholesterolemia, and gender) to rates of radiosurgery-induced obliteration of arteriovenous malformations (AVM). METHODS AND MATERIALS: We evaluated follow-up imaging and clinical data in 329 AVM patients who received gamma knife radiosurgery at the University of Pittsburgh between 1987 and 1994. There were 113 smokers, 29 hypertensives, 5 diabetics, 4 hypercholesterolemics, 159 male patients, and 170 female patients. All patients had regular clinical or imaging follow-up for a minimum of 3 years after radiosurgery. RESULTS: Multivariate analysis showed that smoking had no effect on AVM obliteration (p > 0.43). Hypertension, diabetes, and hypercholesterolemia had no discernible effect on AVM obliteration in this study (p > 0.78). However, females aged 12-49 had a statistically significant lower in-field obliteration rate than males (78% vs. 89%, p = 0.0102). CONCLUSION: Smoking has no effect on AVM obliteration. Hypertension, diabetes, and hypercholesterolemia had no discernible effect in this study. Further study is needed to establish whether estrogen has a vascular protective effect that could partially limit radiosurgical AVM obliteration, as suggested by this study.

Cellular therapies for neurodegenerative diseases.

We are confident that neurodegenerative diseases will be managed by an array of pharmacologic and cellular therapies. These may involve oral or intravenous preparations, surgical cell deliveries, or infusion through cerebral delivery systems. Achievements in neuroscience over the past three decades have redefined some of the rules for basic and clinical research in neurotransplantation. Restorative neurosurgical procedures will develop from different directions, and it is likely that a combination of approaches will be necessary to maximize patient outcomes.

The case for and against AVM radiosurgery.

AVM radiosurgery has been in practice for over 30 years and is now a common method to manage properly selected patients with brain AVMs. The techniques have been refined along with our understanding of the expected response. It is this understanding of expected outcomes that should allow a rational discussion of the pertinent issues for management of patients with AVMs. Some patients will require multimodality approaches. All AVM patients should seek to understand whether stereotactic radiosurgery is an appropriate option for their problem.

Does increased nerve length within the treatment volume improve trigeminal neuralgia radiosurgery? A prospective double-blind, randomized study.

PURPOSE: To test the hypothesis that increasing the nerve length within the treatment volume for trigeminal neuralgia radiosurgery would improve pain relief. METHODS AND MATERIALS: Eighty-seven patients with typical trigeminal neuralgia were randomized to undergo retrogasserian gamma knife radiosurgery (75 Gy maximal dose with 4-mm diameter collimators) using either one (n = 44) or two (n = 43) isocenters. The median follow-up was 26 months (range 1-36). RESULTS: Pain relief was complete in 57 patients (45 without medication and 12 with low-dose medication), partial in 15, and minimal in another 15 patients. The actuarial rate of obtaining complete pain relief (with or without medication) was 67.7% +/- 5.1%. The pain relief was identical for one- and two-isocenter radiosurgery. Pain relapsed in 30 of 72 responding patients. Facial numbness and mild and severe paresthesias developed in 8, 5, and 1 two-isocenter patients vs. 3, 4, and 0 one-isocenter patients, respectively (p = 0.23). Improved pain relief correlated with younger age (p = 0.025) and fewer prior procedures (p = 0.039) and complications (numbness or paresthesias) correlated with the nerve length irradiated (p = 0.018). CONCLUSIONS: Increasing the treatment volume to include a longer nerve length for trigeminal neuralgia radiosurgery does not significantly improve pain relief but may increase complications.