Recommended Resting-State fMRI Acquisition and Preprocessing Steps for Preoperative Mapping of Language and Motor and Visual Areas in Adult and Pediatric Patients with Brain Tumors and Epilepsy.

Resting-state (rs) fMRI has been shown to be useful for preoperative mapping of functional areas in patients with brain tumors and epilepsy. However, its lack of standardization limits its widespread use and hinders multicenter collaboration. The American Society of Functional Neuroradiology, American Society of Pediatric Neuroradiology, and the American Society of Neuroradiology Functional and Diffusion MR Imaging Study Group recommend specific rs-fMRI acquisition approaches and preprocessing steps that will further support rs-fMRI for future clinical use. A task force with expertise in fMRI from multiple institutions provided recommendations on the rs-fMRI steps needed for mapping of language, motor, and visual areas in adult and pediatric patients with brain tumor and epilepsy. These were based on an extensive literature review and expert consensus.Following rs-fMRI acquisition parameters are recommended: minimum 6-minute acquisition time; scan with eyes open with fixation; obtain rs-fMRI before both task-based fMRI and contrast administration; temporal resolution of ≤2 seconds; scanner field strength of 3T or higher. The following rs-fMRI preprocessing steps and parameters are recommended: motion correction (seed-based correlation analysis [SBC], independent component analysis [ICA]); despiking (SBC); volume censoring (SBC, ICA); nuisance regression of CSF and white matter signals (SBC); head motion regression (SBC, ICA); bandpass filtering (SBC, ICA); and spatial smoothing with a kernel size that is twice the effective voxel size (SBC, ICA).The consensus recommendations put forth for rs-fMRI acquisition and preprocessing steps will aid in standardization of practice and guide rs-fMRI program development across institutions. Standardized rs-fMRI protocols and processing pipelines are essential for multicenter trials and to implement rs-fMRI as part of standard clinical practice.

Functional MRI Shows Altered Deactivation and a Corresponding Decrease in Functional Connectivity of the Default Mode Network in Patients with Gliomas.

BACKGROUND AND PURPOSE: The default mode network normally decreases in activity during externally directed tasks. Although default mode network connectivity is disrupted in numerous brain pathologies, default mode network deactivation has not been studied in patients with brain tumors. We investigated default mode network deactivation with language task-based fMRI by measuring the anticorrelation of a critical default mode network node, the posterior cingulate cortex, in patients with gliomas and controls; furthermore, we examined default mode network functional connectivity in these patients with task-based and resting-state fMRI. MATERIALS AND METHODS: In 10 healthy controls and 30 patients with gliomas, the posterior cingulate cortex was identified on task-based fMRI and was used as an ROI to create connectivity maps from task-based and resting-state fMRI data. We compared the average correlation in each default mode network region between patients and controls for each correlation map and stratified patients by tumor location, hemisphere, and grade. RESULTS: Patients with gliomas (P = .001) and, in particular, patients with tumors near the posterior default mode network (P < .001) showed less posterior cingulate cortex anticorrelation in task-based fMRI than controls. Patients with both left- and right-hemisphere tumors, as well as those with grade IV tumors, showed significantly lower posterior cingulate cortex anticorrelation than controls (P = .02, .03, and <.001, respectively). Functional connectivity in each default mode network region was not significantly different between task-based and resting-state maps. CONCLUSIONS: Task-based fMRI showed impaired deactivation of the default mode network in patients with gliomas. The functional connectivity of the default mode network in both task-based and resting-state fMRI in patients with gliomas using the posterior cingulate cortex identified in task-based fMRI as an ROI for seed-based correlation analysis has strong overlap.

[Evaluation of vascular reactivity to overcome limitations of neurovascular uncoupling in BOLD fMRI of malignant brain tumors]. / Otsenka vazoreaktivnosti dlia preodoleniia ogranichenii neirovaskuliarnogo razobshcheniia BOLD fMRT pri zlokachestvennykh opukholiakh golovnogo mozga.

The sensitivity of fMRI in identification of eloquent cortical centers in the case of large infiltrative growing tumors and pronounced peritumoral edema may be reduced or significantly limited in some cases. The main cause is an attenuated Blood-Oxygen-Level-Dependent response (BOLD) caused by pathological vascular reactivity and subsequent neurovascular uncoupling of fMRI. In our study, we attempted to overcome these limitations and increase the sensitivity of this technique in identification of eloquent cortical areas adjacent to brain tumors by using vasoreactivity features of a breath-holding test and including these data in the BOLD analysis. Local vasoreactivity using a breath-holding paradigm with the same block design of both motor and speech tests was determined in 5 healthy volunteers and 3 patients in the preoperative period (two patients with high grade gliomas and one patient with single metastasis). A coherence-based model was developed for analysis of BOLD fMRI, which took into account altered hemodynamics in peritumoral zones. Obtained coherence maps demonstrated clinically more significant activation zones that were not seen with standard methods of fMRI processing. Thus, neurovascular uncoupling that is known to affect the accuracy of the BOLD fMRI response adjacent to brain tumors may be partially overcome by including an independent measurement of vasoreactivity using a breath-holding test in the BOLD analysis.

Differentiating Atypical Hemangiomas and Metastatic Vertebral Lesions: The Role of T1-Weighted Dynamic Contrast-Enhanced MRI.

BACKGROUND AND PURPOSE: Vertebral hemangiomas are benign vascular lesions that are almost always incidentally found in the spine. Their classic typical hyperintense appearance on T1- and T2-weighted MR images is diagnostic. Unfortunately, not all hemangiomas have the typical appearance, and they can mimic metastases on routine MR imaging. These are generally referred to as atypical hemangiomas and can result in misdiagnosis and ultimately additional imaging, biopsy, and unnecessary costs. Our objective was to assess the utility of dynamic contrast-enhanced MR imaging perfusion in distinguishing vertebral atypical hemangiomas and malignant vertebral metastases. We hypothesized that permeability and vascular density will be increased in metastases compared with atypical hemangiomas. MATERIALS AND METHODS: Consecutive patients from 2011 to 2015 with confirmed diagnoses of atypical hemangiomas and spinal metastases from breast and lung carcinomas with available dynamic contrast-enhanced MR imaging were analyzed. Time-intensity curves were qualitatively compared among the groups. Perfusion parameters, plasma volume, and permeability constant were quantified using an extended Tofts 2-compartment pharmacokinetic model. Statistical significance was tested using the Mann-Whitney U test. RESULTS: Qualitative inspection of dynamic contrast-enhanced MR imaging time-intensity curves demonstrated differences in signal intensity and morphology between metastases and atypical hemangiomas. Quantitative analysis of plasma volume and permeability constant perfusion parameters showed significantly higher values in metastatic lesions compared with atypical hemangiomas (P < .001). CONCLUSIONS: Our data demonstrate that plasma volume and permeability constant perfusion parameters and qualitative inspection of contrast-enhancement curves can be used to differentiate atypical hemangiomas from vertebral metastatic lesions. This work highlights the benefits of adding perfusion maps to conventional sequences to improve diagnostic accuracy.

T1-Weighted Dynamic Contrast-Enhanced MR Perfusion Imaging Characterizes Tumor Response to Radiation Therapy in Chordoma.

BACKGROUND AND PURPOSE: Chordomas notoriously demonstrate a paucity of changes following radiation therapy on conventional MR imaging. We hypothesized that dynamic contrast-enhanced MR perfusion imaging parameters of chordomas would change significantly following radiation therapy. MATERIALS AND METHODS: Eleven patients with pathology-proved chordoma who completed dynamic contrast-enhanced MR perfusion imaging pre- and postradiation therapy were enrolled. Quantitative tumor measurements were obtained by 2 attending neuroradiologists. ROIs were used to calculate vascular permeability and plasma volume and generate dynamic contrast-enhancement curves. Quantitative analysis was performed to determine mean and maximum plasma volume and vascular permeability values, while semiquantitative analysis on averaged concentration curves was used to determine the area under the curve. A Mann-Whitney U test at a significance level of P < .05 was used to assess differences of the above parameters between pre- and postradiation therapy. RESULTS: Plasma volume mean (pretreatment mean = 0.82; posttreatment mean = 0.42), plasma volume maximum (pretreatment mean = 3.56; posttreatment mean = 2.27), and vascular permeability mean (pretreatment mean = 0.046; posttreatment mean = 0.028) in the ROIs significantly decreased after radiation therapy (P < .05); this change thereby demonstrated the potential for assessing tumor response. Area under the curve values also demonstrated significant differences (P < .05). CONCLUSIONS: Plasma volume and vascular permeability decreased after radiation therapy, suggesting that these dynamic contrast-enhanced MR perfusion parameters may be useful for monitoring chordoma growth and response to radiation therapy. Additionally, the characteristic dynamic MR signal intensity-time curve of chordoma may provide a radiographic means of distinguishing chordoma from other spinal lesions.

A Novel Methodology for Applying Multivoxel MR Spectroscopy to Evaluate Convection-Enhanced Drug Delivery in Diffuse Intrinsic Pontine Gliomas.

BACKGROUND AND PURPOSE: Diffuse intrinsic pontine gliomas are inoperable high-grade gliomas with a median survival of less than 1 year. Convection-enhanced delivery is a promising local drug-delivery technique that can bypass the BBB in diffuse intrinsic pontine glioma treatment. Evaluating tumor response is critical in the assessment of convection-enhanced delivery of treatment. We proposed to determine the potential of 3D multivoxel (1)H-MR spectroscopy to evaluate convection-enhanced delivery treatment effect in these tumors. MATERIALS AND METHODS: We prospectively analyzed 3D multivoxel (1)H-MR spectroscopy data for 6 patients with nonprogressive diffuse intrinsic pontine gliomas who received convection-enhanced delivery treatment of a therapeutic antibody (Phase I clinical trial NCT01502917). To compare changes in the metabolite ratios with time, we tracked the metabolite ratios Cho/Cr and Cho/NAA at several ROIs: normal white matter, tumor within the convection-enhanced delivery infusion site, tumor outside of the infused area, and the tumor average. RESULTS: There was a comparative decrease in both Cho/Cr and Cho/NAA metabolite ratios at the tumor convection-enhanced delivery site versus tumor outside the infused area. We used MR spectroscopy voxels with dominant white matter as a reference. The difference between changes in metabolite ratios became more prominent with increasing time after convection-enhanced delivery treatment. CONCLUSIONS: The comparative change in metabolite ratios between the convection-enhanced delivery site and the tumor site outside the infused area suggests that multivoxel (1)H-MR spectroscopy, in combination with other imaging modalities, may provide a clinical tool to accurately evaluate local tumor response after convection-enhanced delivery treatment.

Prospective assessment of white matter integrity in adult stem cell transplant recipients.

Hematopoietic stem cell transplantation (HSCT) is often used in the treatment of hematologic disorders. Although it can be curative, the pre-transplant conditioning regimen can be associated with neurotoxicity. In this prospective study, we examined white matter (WM) integrity with diffusion tensor imaging (DTI) and neuropsychological functioning before and one year after HSCT in twenty-two patients with hematologic disorders and ten healthy controls evaluated at similar intervals. Eighteen patients received conditioning treatment with high-dose (HD) chemotherapy, and four had full dose total body irradiation (fTBI) and HD chemotherapy prior to undergoing an allogeneic or autologous HSCT. The results showed a significant decrease in mean diffusivity (MD) and axial diffusivity (AD) in diffuse WM regions one year after HSCT (p-corrected <0.05) in the patient group compared to healthy controls. At baseline, patients treated with allogeneic HSCT had higher MD and AD in the left hemisphere WM than autologous HSCT patients (p-corrected <0.05). One year post-transplant, patients treated with allogeneic HSCT had lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the right hemisphere and left frontal WM compared to patients treated with autologous HSCT (p-corrected <0.05).There were modest but significant correlations between MD values and cognitive test scores, and these were greatest for timed tests and in projection tracts. Patients showed a trend toward a decline in working memory, and had lower cognitive test scores than healthy controls at the one-year assessment. The findings suggest a relatively diffuse pattern of alterations in WM integrity in adult survivors of HSCT.

T1-Weighted Dynamic Contrast-Enhanced MRI as a Noninvasive Biomarker of Epidermal Growth Factor Receptor vIII Status.

BACKGROUND AND PURPOSE: Epidermal growth factor receptor variant III is a common mutation in glioblastoma, found in approximately 25% of tumors. Epidermal growth factor receptor variant III may accelerate angiogenesis in malignant gliomas. We correlated T1-weighted dynamic contrast-enhanced MR imaging perfusion parameters with epidermal growth factor receptor variant III status. MATERIALS AND METHODS: Eighty-two consecutive patients with glioblastoma and known epidermal growth factor receptor variant III status who had dynamic contrast-enhanced MR imaging before surgery were evaluated. Volumes of interest were drawn around the entire enhancing tumor on contrast T1-weighted images and then were transferred onto coregistered dynamic contrast-enhanced MR imaging perfusion maps. Histogram analysis with normalization was performed to determine the relative mean, 75th percentile, and 90th percentile values for plasma volume and contrast transfer coefficient. A Wilcoxon rank sum test was applied to assess the relationship between baseline perfusion parameters and positive epidermal growth factor receptor variant III status. The receiver operating characteristic method was used to select the cutoffs of the dynamic contrast-enhanced MR imaging perfusion parameters. RESULTS: Increased relative plasma volume and increased relative contrast transfer coefficient parameters were both significantly associated with positive epidermal growth factor receptor variant III status. For epidermal growth factor receptor variant III-positive tumors, relative plasma volume mean was 9.3 and relative contrast transfer coefficient mean was 6.5; for epidermal growth factor receptor variant III-negative tumors, relative plasma volume mean was 3.6 and relative contrast transfer coefficient mean was 3.7 (relative plasma volume mean, P < .001, and relative contrast transfer coefficient mean, P = .008). The predictive powers of relative plasma volume histogram metrics outperformed those of the relative contrast transfer coefficient histogram metrics (P < = .004). CONCLUSIONS: Dynamic contrast-enhanced MR imaging shows greater perfusion and leakiness in epidermal growth factor receptor variant III-positive glioblastomas than in epidermal growth factor receptor variant III-negative glioblastomas, consistent with the known effect of epidermal growth factor receptor variant III on angiogenesis. Quantitative evaluation of dynamic contrast-enhanced MR imaging may be useful as a noninvasive tool for correlating epidermal growth factor receptor variant III expression and related tumor neoangiogenesis. This potential may have implications for monitoring response to epidermal growth factor receptor variant III-targeted therapies.

Identification of the Corticobulbar Tracts of the Tongue and Face Using Deterministic and Probabilistic DTI Fiber Tracking in Patients with Brain Tumor.

BACKGROUND AND PURPOSE: The corticobulbar tract of the face and tongue, a critical white matter tract connecting the primary motor cortex and the pons, is rarely detected by deterministic DTI fiber tractography. Detection becomes even more difficult in the presence of a tumor. The purpose of this study was to compare identification of the corticobulbar tract by using deterministic and probabilistic tractography in patients with brain tumor. MATERIALS AND METHODS: Fifty patients with brain tumor who underwent DTI were studied. Deterministic tractography was performed by using the fiber assignment by continuous tractography algorithm. Probabilistic tractography was performed by using a Monte Carlo simulation method. ROIs were drawn of the face and tongue motor homunculi and the pons in both hemispheres. RESULTS: In all subjects, fiber assignment by continuous tractography was ineffectual in visualizing the entire course of the corticobulbar tract between the face and tongue motor cortices and the pons on either side. However, probabilistic tractography successfully visualized the corticobulbar tract from the face and tongue motor cortices in all patients on both sides. No significant difference (P < .08) was found between both sides in terms of the number of voxels or degree of connectivity. The fractional anisotropy of both the face and tongue was significantly lower on the tumor side (P < .03). When stratified by tumor type, primary-versus-metastatic tumors, no differences were observed between tracts in terms of the fractional anisotropy and connectivity values (P > .5). CONCLUSIONS: Probabilistic tractography successfully reconstructs the face- and tongue-associated corticobulbar tracts from the lateral primary motor cortex to the pons in both hemispheres.

Challenges in Identifying the Foot Motor Region in Patients with Brain Tumor on Routine MRI: Advantages of fMRI.

BACKGROUND AND PURPOSE: Accurate localization of the foot/leg motor homunculus is essential because iatrogenic damage can render a patient wheelchair- or bed-bound. We hypothesized the following: 1) Readers would identify the foot motor homunculus <100% of the time on routine MR imaging, 2) neuroradiologists would perform better than nonradiologists, and 3) those with fMRI experience would perform better than those without it. MATERIALS AND METHODS: Thirty-five attending-level raters (24 neuroradiologists, 11 nonradiologists) evaluated 14 brain tumors involving the frontoparietal convexity. Raters were asked to identify the location of the foot motor homunculus and determine whether the tumor involved the foot motor area and/or motor cortex by using anatomic MR imaging. Results were compared on the basis of prior fMRI experience and medical specialty by using Mann-Whitney U test statistics. RESULTS: No rater was 100% correct. Raters correctly identified whether the tumor was in the foot motor cortex 77% of the time. Raters with fMRI experience were significantly better than raters without experience at foot motor fMRI centroid predictions (13 ± 6 mm versus 20 ± 13 mm from the foot motor cortex center, P = 2 × 10(-6)) and arrow placement in the motor gyrus (67% versus 47%, P = 7 × 10(-5)). Neuroradiologists were significantly better than nonradiologists at foot motor fMRI centroid predictions (15 ± 8 mm versus 20 ± 14 mm, P = .005) and arrow placement in the motor gyrus (61% versus 46%, P = .008). CONCLUSIONS: The inability of experienced readers to consistently identify the location of the foot motor homunculus on routine MR imaging argues for using fMRI in the preoperative setting. Experience with fMRI leads to improved accuracy in identifying anatomic structures, even on routine MR imaging.

A prospective evaluation of changes in brain structure and cognitive functions in adult stem cell transplant recipients.

Hematopoietic stem cell transplantation (HSCT) is an efficacious treatment for many hematologic malignancies. However, the conditioning regimen of high-dose (HD) chemotherapy with or without total body irradiation (TBI) can be associated with neurotoxicity. In this prospective study, we used quantitative neuroimaging techniques to examine regional gray matter and ventricular volumes, and standardized neuropsychological tests to assess cognitive function before and 1 year after HSCT in 28 patients with hematologic malignancies and in ten healthy controls evaluated at similar intervals. Nineteen patients received conditioning treatment with HD chemotherapy alone and nine had both TBI and HD chemotherapy. There was a significant reduction in gray matter volume in the middle frontal gyrus bilaterally and in the left caudate nucleus in the patient group (all patients combined) but not among healthy controls over the 1-year follow-up period. There was a significant increase in left lateral ventricle volume and in total ventricle volume in the patient group, relative to healthy controls. Similar brain structural changes were seen for patients treated with HD chemotherapy alone. The neuropsychological results showed that 21% of patients could be classified as impaired at baseline. The Reliable Change Index suggested no significantly different rates of cognitive decline between patients and healthy controls. The findings suggest that HSCT patients may be at an increased risk for developing regional brain volume loss, and that subgroups may experience cognitive dysfunction prior to and 1 year following the transplant.

Characterizing hypervascular and hypovascular metastases and normal bone marrow of the spine using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: The role of DCE-MR imaging in the study of bone marrow perfusion is only partially developed, though potential applications for routine use in the clinical setting are beginning to be described. We hypothesize that DCE-MR imaging can be used to discriminate between hypervascular and hypovascular metastases based on measured perfusion variables. MATERIALS AND METHODS: We conducted a retrospective study of 26 patients using conventional MR imaging and DCE-MR imaging. Patients were assigned to a hypervascular or hypovascular group based on tumor pathology. ROIs were drawn around normal-appearing bone marrow (internal controls) and enhancing tumor areas. Average wash-in enhancement slope, average peak enhancement signal percentage change, and average peak enhancement signal percentage change in areas of highest wash-in enhancement slope were calculated. Indices were compared among control, hypervascular, and hypovascular groups. Conventional imaging was assessed by calculating pre- to postgadolinium signal percentage changes in hypervascular and hypovascular lesions. RESULTS: Hypervascular and hypovascular tumors differed significantly with regard to wash-in enhancement slope (P < .01; hypervascular 95% CI, 22.5-26.5 AU/s; hypovascular 95% CI, 14.1-20.9 AU/s) and peak enhancement signal percentage change in areas of highest wash-in enhancement slope (P < .01; hypervascular 95% CI, 174.1-323.3%; hypovascular 95% CI, 39.5-150.5%). Peak enhancement signal percentage change over all voxels was not significant (P = .62). Areas of normal-appearing marrow showed no appreciable contrast enhancement. Conventional contrast-enhanced MR imaging was unable to differentiate between hypervascular and hypovascular tumors (P = .58). CONCLUSIONS: Our data demonstrate that, unlike conventional MR imaging sequences, DCE-MR imaging may be a more accurate technique in discriminating hypervascular from hypovascular spinal metastases.

Somatotopic organization of motor pathways in the internal capsule: a probabilistic diffusion tractography study.

BACKGROUND AND PURPOSE: The location of the motor pathways in the PLIC remains controversial. In the current study, we trace the fibers from the tongue, face, hand, and foot motor cortices by using probabilistic diffusion tractography and define their somatotopic organization in the PLIC. MATERIALS AND METHODS: Twenty subjects were retrospectively studied. Fiber tracts were separately calculated between ROIs in the cerebral peduncle and in the 4 different motor regions in the precentral gyrus. Probabilistic connectivity maps were generated, and the voxel with the highest probability was designated as the position of the motor pathway. The PI and LI were defined as the relative anteroposterior and mediolateral locations of the motor pathways. RESULTS: Tongue pathways were located anteromedial to face in 16 hemispheres (40%), with P < .05 for the PI and LI. Face pathways were located anteromedial to hand in 25 hemispheres (62.5%) with P < .05 for PI and LI. Hand pathways were anteromedial to foot in 14 hemispheres (35%) and anterior in 11 hemispheres (27.5%), with P < .05 for PI but P > .13 for LI. Group analysis showed that the somatotopic arrangement of the bilateral hemispheres was symmetric. CONCLUSIONS: Probabilistic tractography demonstrated the anteroposterior alignment of the motor pathways along the long axis in the PLIC. Probabilistic tractography successfully tracked the motor pathways of the tongue, face, hand, and foot from the precentral gyrus through their intersection with the larger superior longitudinal fasciculus to the PLIC in all cases, overcoming limitations of standard (nonprobabilistic) tractography methods.

Assessment of the language laterality index in patients with brain tumor using functional MR imaging: effects of thresholding, task selection, and prior surgery.

BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) is used to determine preoperatively the laterality of cortical language representation along with the relationship of language areas to adjacent brain tumors. The purpose of this study was to determine whether changing the statistical threshold for different language tasks influences the language laterality index (LI) for a group of controls, patients with tumor without prior surgery, and patients with tumor and prior surgery. MATERIALS AND METHODS: Seven controls, 9 patients with tumor without prior surgery, and 4 patients with tumor and prior surgery performed verb-generation, phonemic fluency, and semantic fluency language tasks during fMRI. Interhemispheric activation differences between the left and right Broca regions of interest were determined by calculating language LIs. LIs were compared within each group, between groups, and between language tasks. Intraoperative electrocortical mapping or the presence of aphasia during postoperative neurology examinations or both were used as ground truth. RESULTS: The language LI varied as a result of statistical thresholding, presence of tumor, prior surgery, and language task. Although patients and controls followed a similar shape in the LI curve, there was no optimal P value for determining the LI. Three patients demonstrated a shift in the LI between hemispheres as a function of statistical threshold. Verb generation was the least variable task both between tasks and across groups. CONCLUSION: For preoperative patients with tumor, the LI should be examined across a spectrum of P values and a range of tasks to ensure reliability. Our data suggest that the LI may be threshold- and task-dependent, particularly in the presence of adjacent tumor.

A pilot study of event-related functional magnetic resonance imaging of monitored wrist movements in patients with partial recovery.

BACKGROUND AND PURPOSE: Previous functional imaging studies of motor recovery after stroke have investigated cerebral activation during periods of repetitive, often complex, movement. This article reports the use of an event-related approach to study activation associated with isolated simple movements (wrist extension). This allows investigation of the pattern of the motor response and corresponding brain activation on a trial-by-trial basis. Patients with partial recovery can be assessed, and allowance can be made for abnormalities in the shape of hemodynamic responses. METHODS: Functional MRI at 3 T was performed during a series of isolated, near-isometric wrist extension movements. A visual tracking procedure was used to elicit forces of 10% and 20% of maximum voluntary contraction. Force output from both wrists was monitored continuously. A voxel-wise procedure was used to fit the optimum hemodynamic response functions in each case. RESULTS: Three chronic stage patients with partial recovery were successfully scanned and compared with 8 healthy controls. The patients showed well-lateralized motor responses but inaccurate control of force. During movement of the paretic wrist, we observed excessive activation of the ipsilateral primary motor cortex and increased relative activation of the supplementary motor area compared with movement of the nonparetic side. In the primary motor area, hemodynamic responses peaked more quickly on the ipsilateral side in 2 patients for movements of the paretic hand, whereas controls showed the opposite trend. CONCLUSIONS: An event-related approach can be used to study the relationship between motor responses and cerebral activation in patients with partial recovery. These preliminary findings suggest that excessive activation in ipsilateral motor cortex and secondary motor areas remains evident under these tightly controlled conditions and cannot be ascribed to mirror movements or abnormalities in the timing of the blood oxygen level-dependent (BOLD) response. However, close monitoring of motor responses also makes evident continuing impairment in motor skill, which makes comparison with activation in normal controls difficult.

Cerebral activation during a simple force production task: changes in the time course of the haemodynamic response.

An event-related paradigm was used to investigate the fMRI signal from the primary motor cortex (M1) and the supplementary motor area (SMA) during isolated isometric wrist extension at five different force levels. There was only a weak trend towards increased area of activation with increased force output, but there was a force-related increase in percentage change of signal within voxels in M1 (Kendall Tc = 0.48, p < 0.01), which may indicate control of force output by variation of neural firing rate. In SMA there was a correlation between peak force output and time-to-peak of the haemodynamic response in SMA (Kendall Tc = 0.74, p < 0.0001). This unexpected finding of a task-related change in the shape of the haemodynamic response within a single brain area requires further investigation. It may indicate a slower rise time at lower perfusion rates, or may be the result of inhibitory processes in motor control.

Reconstruction of 6 MV photon spectra from measured transmission including maximum energy estimation.

Photon spectra from a nominally 6 MV beam under standard clinical conditions and at higher and lower beam qualities have been derived from narrow-beam transmission measurements using a previously published three-parameter reconstruction model. Estimates of the maximum photon energy present in each spectrum were derived using a reduced number of model parameters. An estimate of the maximum contribution of background, or room, scatter to transmission measurements has been made for this study and is shown to be negligible in terms of the quality index and percentage depth-dose of the derived spectra. Percentage depth-dose data for standard beam conditions derived from the reconstructed spectrum were found to agree with direct measurements to within approximately 1% for depths of up to 25 cm in water. Quality indices expressed in terms of TPR10(20) for all spectra were found to agree with directly measured values to within 1%. The experimental procedure and reconstruction model are therefore shown to produce photon spectra whose derived quality indices and percentage depth-dose values agree with direct measurement to within expected experimental uncertainty.