Biomedical subjects

C Studholme

Publications and source records attributed to C Studholme.

At least 19 recordsLinked to original sources

PubMed2006

Comprehensive processing, display and analysis for in vivo MR spectroscopic imaging.

Image reconstruction for magnetic resonance spectroscopic imaging (MRSI) requires specialized spatial and spectral data processing methods and benefits from the use of several sources of prior information that are not commonly available, including MRI-derived tissue segmentation, morphological analysis and spectral characteristics of the observed metabolites. In addition, incorporating information obtained from MRI data can enhance the display of low-resolution metabolite images and multiparametric and regional statistical analysis methods can improve detection of altered metabolite distributions. As a result, full MRSI processing and analysis can involve multiple processing steps and several different data types. In this paper, a processing environment is described that integrates and automates these data processing and analysis functions for imaging of proton metabolite distributions in the normal human brain. The capabilities include normalization of metabolite signal intensities and transformation into a common spatial reference frame, thereby allowing the formation of a database of MR-measured human metabolite values as a function of acquisition, spatial and subject parameters. This development is carried out under the MIDAS project (Metabolite Imaging and Data Analysis System), which provides an integrated set of MRI and MRSI processing functions. It is anticipated that further development and distribution of these capabilities will facilitate more widespread use of MRSI for diagnostic imaging, encourage the development of standardized MRSI acquisition, processing and analysis methods and enable improved mapping of metabolite distributions in the human brain.

Algorithms↗

PubMed2006

MR imaging anatomy in neurodegeneration: a robust volumetric parcellation method of the frontal lobe gyri with quantitative validation in patients with dementia.

BACKGROUND AND PURPOSE: Brain volumetry is widely used for evaluating tissue degeneration; however, the parcellation methods are rarely validated and use arbitrary planes to mark boundaries of brain regions. The goal of this study was to develop, validate, and apply an MR imaging tracing method for the parcellation of 3 major gyri of the frontal lobe, which uses only local landmarks intrinsic to the structures of interest, without the need for global reorientation or the use of dividing planes or lines. METHODS: Studies were performed on 25 subjects--healthy controls and subjects diagnosed with Lewy body dementia and Alzheimer disease--with significant variation in the underlying gyral anatomy and state of atrophy. The protocol was evaluated by using multiple observers tracing scans of subjects diagnosed with neurodegenerative disease and those aging normally, and the results were compared by spatial overlap agreement. To confirm the results, observers marked the same locations in different brains. We illustrated the variabilities of the key boundaries that pose the greatest challenge to defining consistent parcellations across subjects. RESULTS: The resulting gyral volumes were evaluated, and their consistency across raters was used as an additional assessment of the validity of our marking method. The agreement on a scale of 0-1 was found to be 0.83 spatial and 0.90 volumetric for the same rater and 0.85 spatial and 0.90 volumetric for 2 different raters. The results revealed that the protocol remained consistent across different neurodegenerative conditions. CONCLUSION: Our method provides a simple and reliable way for the volumetric evaluation of frontal lobe neurodegeneration and can be used as a resource for larger comparative studies as well as a validation procedure of automated algorithms.

Aged↗

PubMed2005

A novel approach to high resolution fetal brain MR imaging.

This paper describes a novel approach to forming high resolution MR images of the human fetal brain. It addresses the key problem of motion of the fetus by proposing a registration refined compounding of multiple sets of orthogonal fast 2D MRI slices, that are currently acquired for clinical studies, into a single high resolution MRI volume. A robust multi-resolution slice alignment is applied iteratively to the data to correct motion of the fetus that occurs between 2D acquisitions. This is combined with an intensity correction step and a super resolution reconstruction step, to form a single high isotropic resolution volume of the fetal brain. Experimental validation on synthetic image data with known motion types and underlying anatomy, together with retrospective application to sets of clinical acquisitions are included. Results indicate the method promises a unique route to acquiring high resolution MRI of the fetal brain in vivo allowing comparable quality to that of neonatal MRI. Such data is highly valuable in allowing a clinically applicable window into the process of normal and abnormal brain development.

Algorithms↗

PubMed2005

Quantitative brain MRI in alcohol dependence: preliminary evidence for effects of concurrent chronic cigarette smoking on regional brain volumes.

BACKGROUND: Recent in vivo research using magnetic resonance spectroscopy demonstrated that chronic cigarette smoking exacerbates regional chronic alcohol-induced brain injury. Other studies associated cigarette smoking with gray matter volume reductions in healthy adults, with greater brain atrophy in aging, and with poorer neurocognition. Although cigarette smoking is common among alcohol-dependent individuals, previous research did not account for the potential effects of chronic smoking on regional brain volumes in alcoholism. METHODS: High-resolution T1-weighted magnetic resonance images from one-week-abstinent, alcohol-dependent individuals and light drinkers were automatically segmented into gray matter, white matter, and cerebral spinal fluid of lobes and subcortical structures. A brief neuropsychological test battery was used to assess cognition in alcohol-dependent individuals. The alcoholic and nondrinking groups were retrospectively divided into chronic smokers and nonsmokers, and the volumetric data were analyzed as a function of alcohol and smoking status. RESULTS: Chronic alcohol dependence was associated with smaller volumes of frontal and parietal white matter, parietal and temporal gray matter, and thalami, accompanied by widespread sulcal but not ventricular enlargements. Chronic cigarette smoking was associated with less parietal and temporal gray matter and with more temporal white matter. Among alcoholics, better visuospatial learning and memory and greater visuomotor scanning speed were correlated with larger lobar white matter volumes in the nonsmoking alcohol-dependent group only. CONCLUSIONS: These data provide preliminary evidence that comorbid chronic cigarette smoking accounts for some of the variance associated with cortical gray matter loss and appears to alter relationships between brain structure and cognitive functions in alcohol-dependent individuals.

Adult↗

PubMed2004

Deformation tensor morphometry of semantic dementia with quantitative validation.

High-resolution structural MRI scans of 20 subjects diagnosed with semantic dementia were compared against scans of 20 cognitively normal control subjects using whole brain deformation tensor morphometry to study spatially consistent differences in local anatomical size. A fine lattice free-form volume registration algorithm was used to estimate a continuous mapping from a reference MRI to each individual subject MRI. The Jacobian of these transformations at each voxel were used to quantitatively map relative anatomical size in each individual brain. Intensity consistent filtering was applied to the determinant of these Jacobians. A careful validation using manually traced gyral anatomy was carried out and used to select an optimal deformation tensor filter scale at which to examine the anatomical size maps. General linear modeling at each voxel was used to decompose the influence of age and head size from the primary diagnosis. Maps of the T statistic of the diagnosis across the 40 subjects highlighted significant (P < 0.01 Bonferroni corrected) focal tissue contraction effects related to dementia diagnosis in the left temporal pole extending into the hippocampus, occipitotemporal gyrus and parahippocampal gyrus. Some evidence of greater focal contraction in gray over white matter was also apparent. Contraction effects were also seen, but with reduced significance in the right temporal anatomy, focused toward the temporal pole and hippocampal regions. Additional lower significance findings (P < 0.05 permutation corrected) were detected in the left superior frontal gyrus, left orbital gyrus and left parietal lobe.

Aged↗

PubMed2004

Effects of heavy drinking, binge drinking, and family history of alcoholism on regional brain metabolites.

BACKGROUND: The main goals are to investigate the effects of chronic active heavy drinking on N-acetylaspartate (NAA) and other metabolites throughout the brain and to determine whether they are affected by family history (FH) of alcoholism and long-term drinking pattern. METHODS: Forty-six chronic heavy drinkers (HD) and 52 light drinkers (LD) were recruited from the community and compared on measures of regional brain structure using magnetic resonance imaging and measures of common brain metabolites in gray matter (GM) and white matter (WM) of the major lobes, subcortical nuclei, brainstem, and cerebellum using short-echo time magnetic resonance spectroscopic imaging. Regional atrophy-corrected levels of NAA, myoinositol (mI), creatine, and choline-containing metabolites were compared as a function of group, FH of alcoholism, and bingeing. RESULTS: Frontal WM NAA was lower in FH-negative HD than FH-positive HD and tended to be lower in women than men. Creatine-containing metabolites in parietal GM were higher in HD than LD. FH-negative compared with FH-positive HD also had more mI in the brainstem and tended to have lower NAA and more mI in frontal GM. Although parietal GM NAA was not significantly lower in HD than LD, it was lower in non-binge drinkers than bingers. Frontal WM NAA was lower in HD than LD, with the difference driven by a small number of women, FH-negative HD, and older age. Lower frontal WM NAA in HD was associated with lower executive and working memory functions and with lower P3b amplitudes at frontal electrodes. CONCLUSIONS: Community-dwelling HD who are not in alcoholism treatment have brain metabolite changes that are associated with lower brain function and are likely of behavioral significance. Age, FH, and binge drinking modulate brain metabolite abnormalities. Metabolite changes in active HD are less pronounced and present with a different spatial and metabolite pattern than reported in abstinent alcoholics.

Adult↗

PubMed2004

Accurate template-based correction of brain MRI intensity distortion with application to dementia and aging.

This paper examines an alternative approach to separating magnetic resonance imaging (MRI) intensity inhomogeneity from underlying tissue-intensity structure using a direct template-based paradigm. This permits the explicit spatial modeling of subtle intensity variations present in normal anatomy which may confound common retrospective correction techniques using criteria derived from a global intensity model. A fine-scale entropy driven spatial normalisation procedure is employed to map intensity distorted MR images to a tissue reference template. This allows a direct estimation of the relative bias field between template and subject MR images, from the ratio of their low-pass filtered intensity values. A tissue template for an aging individual is constructed and used to correct distortion in a set of data acquired as part of a study on dementia. A careful validation based on manual segmentation and correction of nine datasets with a range of anatomies and distortion levels is carried out. This reveals a consistent improvement in the removal of global intensity variation in terms of the agreement with a global manual bias estimate, and in the reduction in the coefficient of intensity variation in manually delineated regions of white matter.

Aging↗

PubMed2003

An intensity consistent filtering approach to the analysis of deformation tensor derived maps of brain shape.

Deformation tensor morphometry makes use of the derivatives of spatial transformations between anatomies, to provide highly localized volumetric maps of relative anatomical size. The analysis of such maps, however, has the challenge of describing the data in a way that allows the spatial scale and extent of the local shape properties to match those induced by the disease process being studied. This study examines an approach to the spatial filtering of transformation Jacobian maps created in multisubject studies of brain anatomy, which constrains the filter neighborhood within common structural boundaries present in the spatially normalized image data. The filtering incorporates information derived from the spatial normalization process, using a statistical framework to introduce a measure of uncertainty in local regional intensity correspondence following spatial normalisation. The proposed filtering approach is compared to the use of spatially invariant Gaussian filtering in the analysis of Jacobian determinant maps of brain shape and shape change in Alzheimer's disease and normal aging. Results show significantly improved delineation of fine scale patterns of shape difference (in cross-sectional studies) and shape change (from multiple serial magnetic resonance imaging studies).

Age Factors↗

PubMed2001

Transplantation of articular cartilage following a step-cooling cryopreservation protocol.

Using a step-cooling cryopreservation protocol that held the tissue 60 min at -4 degrees C, 30 min at -8 degrees C, and 10 min at -40 degrees C before plunging into liquid nitrogen, we were able to get a substantial improvement in the magnitude and pattern of chondrocyte recovery following cryopreservation, achieving postthaw recoveries of 62 +/- 13%. These results are consistent with the hypothesis that ice growth within articular cartilage is planar, but they provide no direct support for that hypothesis. Transplanting (step-cooled) cryopreserved osteochondral allografts into adult Suffolk/Romanoff crossbred sheep for periods of 3 months and 1 year further tested the efficacy of the cryopreservation protocol. Unfortunately, the cryoinjury sustained by the chondrocytes during cryopreservation, although apparently nonlethal immediately after thawing in many cases, was not innocuous in the long term. The presence of large clusters of chondrocytes at 1 year after transplantation illustrates that cryoinjury not detectable with a membrane integrity assay can still have far-reaching effects on transplanted tissue.

Animals↗

PubMed2001

Estimating tissue deformation between functional images induced by intracranial electrode implantation using anatomical MRI.

This paper examines a solution to the general problem of accurately relating points within functional data acquired before and after subdural intracranial electrode implantation. We develop an approach based on nonrigid registration of high resolution anatomical MRI acquired together with the functional data. This makes use of a free-form B-Spline deformation model and registration is recovered by maximizing the normalized mutual information between the preimplant MRI and the postimplant MRI. We apply the approach to estimate the tissue deformation induced by the presence of intracranial electrodes over 15 patient studies. Maximum tissue displacements of 4 mm or greater were observed in all cases either in the cortex or around the ventricles due to CSF loss. In studies involving larger 4 x 4 grids, local tissue displacement estimates exceeded 10 mm from the preimplant brain shape. The key issue with this approach is whether the deformation estimates are contaminated by the presence of susceptibility-induced imaging artifacts. We therefore evaluate the deformation estimates in recovering alignment of essentially identical SPECT studies of eight patients acquired before and after electrode placement. An ROI-based analysis of the variance of resulting subtraction values between pre- and postimplant SPECT was carried out in regions of tissue below electrode grids. Results indicate for all cases a substantial reduction in residual SPECT subtraction artifacts to a level comparable to that in an equivalent region of undeformed tissue.

Adolescent↗

PubMed2001

Interictal 99mTc-HMPAO SPECT in temporal lobe epilepsy: relation to clinical variables.

PURPOSE: Factors affecting blood flow observed by interictal single-photon emission computed tomography (SPECT) images in temporal lobe epilepsy (TLE) have not been systematically studied or consistently demonstrated. We evaluated interictal SPECT results with respect to many clinical variables in a large population of TLE patients, all of whom underwent temporal lobectomy. METHODS: Interictal 99mTc-HMPAO SPECT scans from 61 TLE patients were obtained before an anterior temporal lobectomy. SPECT was analyzed using a region of interest analysis (ROI) in the cerebellum, anterior temporal lobe, lateral temporal lobe, mesial temporal lobe, whole temporal lobe, and inferior frontal lobe. Asymmetry indices (AIs) were calculated. Correlative analysis of AIs and clinical variables was performed. RESULTS: The AIs from TLE patients differed significantly from those of controls in the anterior temporal (p < 0.01), lateral temporal (p < 0.001), and whole temporal (p < 0.01) regions. No consistent overall correlation between the AIs and clinical variables existed. In right TLE (RTLE) only, AIs in the lateral and whole temporal lobe were positively correlated with age of onset (r = 0.470, p < 0.05; r = 0.548, p < 0.01, respectively). Similarly, in RTLE only, duration of epilepsy was negatively correlated with the anterior (r = -0.395, p < 0.05) and mesial (r = -0.45, p < 0.05) temporal lobe AI. No correlations were found between clinical variables and AIs in left TLE (LTLE) patients. CONCLUSIONS: Significant correlation of age at onset and duration of epilepsy with AIs in RTLE but not LTLE suggests physiologic processes may be determined in part by laterality of TLE. Clinical applications are problematic.

Adult↗

PubMed2001

Functional MRI of language processing: dependence on input modality and temporal lobe epilepsy.

PURPOSE: Functional magnetic resonance imaging (MRI) using two language-comprehension tasks was evaluated to determine its ability to lateralize language processing and identify regions that must be spared in surgery. METHODS: Two parallel cognitive language tasks, one using auditory input and the other visual input, were tested in a group of control subjects and in temporal lobe epilepsy patients who were candidates for surgical intervention. The patient studies provide an opportunity to compare functional MRI language localization with that obtained using Wada testing and electrocorticography. All of the patients in this study underwent all three procedures and a battery of neuropsychological testing. Such studies provide an opportunity not only to validate the fMRI findings but also, by comparing the patient results with those obtained in control subjects, to provide insight into the impact of a pathology such as epilepsy on cortical organization or functional patterns of activation. RESULTS: The results reveal both modality-dependent and modality-independent language-processing patterns for visual versus auditory task presentation. The visual language task activated distinct sites in Broca's area, BA (Brodmann area) 44 that were not activated in the auditory language task. The auditory language task strongly activated contralateral right BA22-21 area (homologous to Wernicke's area on the left). Language lateralization scores were significantly stronger for visual than for auditory task presentation. The conjunction of activation from the two different input modalities (modality-independent areas) likely highlights regions that perform more abstract computations (e.g., syntactic or pragmatic processing) in language processing. Modality-specific areas (e.g., right Wernicke, left fusiform gyrus, Broca BA44, supramarginal gyrus), appear to cope with the computations relevant to making contact with these more abstract dimensions. Patients showed recruitment of contralateral homologous language areas (p < 0.005) that was significantly above that found in a normal control group. Extra- and intraoperative cortical stimulations were concordant with the fMRI data in eight of 10 cases. The fMRI lateralization scores were also consistent with the Wada testing in 8/10 patients. CONCLUSIONS: The fMRI results demonstrate that the epileptic brain may be a progressive model for cortical plasticity.

Adult↗

PubMed2000

Reproducibility of serial peri-ictal single-photon emission tomography difference images in epilepsy patients undergoing surgical resection.

Peri-ictal single-photon emission tomography (SPET) difference images co-registered to magnetic resonance imaging (MRI) visualize regional cerebral blood flow (rCBF) changes and help localize the epileptogenic area in medically refractory epilepsy. Few reports have examined the reproducibility of SPET difference image results. Epilepsy patients having two peri-ictal and at least one interictal SPET scan who later underwent surgical resection were studied. Localization accuracy of peri-ictal SPET difference images results, interictal electroencephalography (EEG), and ictal EEG from the first (seizure 1) and second (seizure 2) seizure, as well as MRI and positron emission tomography (PET) findings, were compared using surgical resection site as the standard. Thirteen patients underwent surgical resection (11 temporal lobe and 2 extratemporal). SPET results from seizure 1 were localized to the surgical site in 12/13 (92%) patients, while SPET results from seizure 2 were localized in 13/13 (100%) patients. All other modalities were less accurate than the SPET results interictal EEG--seizure 1 6/13 (46%); ictal EEG--seizure 1 5/13 (38%); interictal intracranial EEG--seizure 2 4/9 (44%); ictal intracranial EEG--seizure 2 results 8/9 (89%); MRI 6/13 (46%); PET 9/13 (69%)[. SPET results were reproducible in 12/13 (92%) patients. SPET difference images calculated from two independent peri-ictal scans appear to be reproducible and accurately localize the epileptogenic area. While SPET difference images visualize many areas of rCBF change, the quantification of these results along with consideration of injection time improves the diagnostic interpretation of the results.

Adult↗

PubMed2000

The alpha-2A-adrenoceptor agonist, guanfacine, increases regional cerebral blood flow in dorsolateral prefrontal cortex of monkeys performing a spatial working memory task.

Research indicates that norepinephrine enhances the working memory functions of the prefrontal cortex (PFC) through actions at post-synaptic, alpha-2A adrenoceptors. The current study examined the effects of the alpha-2A adrenoreceptor agonist, guanfacine (0.7 mg/kg, i.m.), compared to saline on SPECT measures of regional cerebral blood flow (rCBF) in monkeys performing a spatial working memory task. Animals were infused with the SPECT blood flow tracer, Tcm-99m ECD, through an indwelling intravenous catheter while performing the working memory task. Guanfacine treatment significantly improved cognitive performance of the working memory task, and significantly increased rCBF values in the dorsolateral PFC, the brain region most tightly associated with performance of spatial working memory tasks. In contrast, guanfacine had no significant effect on rCBF in the superior temporal cortex, an auditory association area unrelated to task performance. These data are consistent with the hypothesis that alpha-2A adrenoceptor stimulation preferentially enhances functioning of the PFC.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2000

Decreased cerebral blood flow during seizures with ictal SPECT injections.

Increased regional cerebral blood flow (rCBF) at the epileptogenic site has been consistently reported for single photon emission computed tomography (SPECT) injections made during seizure activity, and the increased rCBF has been shown to remain elevated at the epileptogenic site in some cases, even when SPECT injections are made after seizure termination (postictal). A sustained increase in rCBF after seizure cessation was recently confirmed, but for no more than 100 s from seizure onset [Avery, R.A., Spencer, S.S., Spanaki, M.V., Corsi, M., Seibyl, J.P., Zubal, I.G., 1999. Effect of injection time on postictal SPET perfusion changes in medically refractory epilepsy. Eur. J. Nucl. Med. 26, 830-836]. In the current study, it is examined whether ictal SPECT injections demonstrate a similar change in rCBF around 100 s from seizure onset. Twenty-one patients with medically refractory epilepsy and a known area of seizure onset receiving ictal and interictal 99mTc-Hexamethyl-propyleneamineoxime (HMPAO) SPECT scans were studied. The results of SPECT subtraction analysis which visualize increased and decreased rCBF were compared to seizure duration and HMPAO injection time. Five patients received ictal SPECT injections (during ongoing seizure activity) more than 90 s after seizure onset and demonstrated decreased rCBF. Two of these patients also demonstrated areas of increased rCBF. Decreased rCBF was localized to the epileptogenic lobe in four of the five patients. By examining ictal SPECT injections made 90 s after seizure onset, evidence was found that reduced rCBF may exist during ictus. The change in rCBF around 90 s is also observed in postictal injections, suggesting a common metabolic mechanism may be responsible.

Adolescent↗

PubMed2000

Accurate alignment of functional EPI data to anatomical MRI using a physics-based distortion model.

Mapping of functional magnetic resonance imaging (fMRI) to conventional anatomical MRI is a valuable step in the interpretation of fMRI activations. One of the main limits on the accuracy of this alignment arises from differences in the geometric distortion induced by magnetic field inhomogeneity. This paper describes an approach to the registration of echo planar image (EPI) data to conventional anatomical images which takes into account this difference in geometric distortion. We make use of an additional spin echo EPI image and use the known signal conservation in spin echo distortion to derive a specialized multimodality nonrigid registration algorithm. We also examine a plausible modification using log-intensity evaluation of the criterion to provide increased sensitivity in areas of low EPI signal. A phantom-based imaging experiment is used to evaluate the behavior of the different criteria, comparing nonrigid displacement estimates to those provided by a imagnetic field mapping acquisition. The algorithm is then applied to a range of nine brain imaging studies illustrating global and local improvement in the anatomical alignment and localization of fMRI activations.

Algorithms↗

PubMed2000

Ratio-images calculated from interictal positron emission tomography and single-photon emission computed tomography for quantification of the uncoupling of brain metabolism and perfusion in epilepsy.

PURPOSE: Image processing techniques were applied to interictal positron emission tomography (PET) and single-photon emission computed tomography (SPECT) brain images to aid in the localization of epileptogenic foci by calculating a functional image that represents the degree of coupling between perfusion and metabolism. Uncoupling of these two functions has been demonstrated to be a characteristic of epileptogenic tissue in temporal lobe epilepsy and has the potential to serve as a diagnostic measure for localization in other areas as well. METHODS: Interictal PET ((18)F-FDG) and interictal SPECT ((99m)Tc-HMPAO) scans were acquired from 11 epilepsy patients. The metabolism and perfusion images were three-dimensionally spatially registered, and a functional ratio-image was computed. These functional maps are overlaid onto a three-dimensional rendering of the same patient's magnetic resonance imaging anatomy. RESULTS: In all patients, an average uniform perfusion-to-metabolism ratio showed approximately constant values throughout most of the whole brain. However, the epileptogenic area (confirmed on surgery) demonstrated an area of elevated perfusion/metabolism in the grey matter. CONCLUSIONS: Although hypometabolism in the PET image was observed in most of these patients, the calculation of a functional ratio-image demonstrated localized foci that in some cases could not be observed on the PET image alone. The ratio-image also yields a quantitative measure of the uncoupling phenomenon.

Adolescent↗

PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗