Feasibility of performance-based functional assessment in brain tumour survivors.

INTRODUCTION: Rehabilitation and exercise interventions are beneficial for the physical and psychological health of cancer survivors. Current clinic-based performance status measures do not accurately capture the survivor's functioning, or rehabilitation and exercise needs. Our primary objective was to explore the feasibility of performing a performance-based functional assessment with brain tumour survivors as a means to inform needs for rehabilitation and exercise. METHODS: A feasibility study was conducted with survivors of brain and other neurological cancers attending new patient or follow-up clinics. Survivors were assessed using the Short Physical Performance Battery (SPPB), grip strength and Rosow-Breslau Physical Activity Self-Assessment (RSB). RESULTS: We approached 40 survivors with brain tumours, and 30 agreed to participate in the study. The SPPB was inversely correlated with Eastern Cooperative Oncology Group (ECOG) scores (r = -.73; p < .01), but scores on the SPPB for individuals classified as ECOG 1 ranged from 5 to 12 out of 12, indicating a large variability in functional scores within this ECOG grade. CONCLUSION: Implementation of objective functional testing is feasible in the neuro-oncology outpatient clinic. The SPPB appears to best inform the functional status of survivors with brain tumours, facilitating more individualised exercise and rehabilitation referrals.

4D blood flow model for dose calculation to circulating blood and lymphocytes.

To better understand how radiotherapy delivery parameters affect the depletion of circulating lymphocytes in patients treated for intra-cranial tumors, we developed a computational human body blood flow model (BFM), that enables to estimate the dose to the circulating blood during the course of fractionated radiation therapy. A hemodynamic cardiovascular system based on human body reference values was developed to distribute the cardiac output to 24 different organs, described by a discrete Markov Chain. For explicit intracranial blood flow modeling, we extracted major cerebral vasculature from MRI data of a patient and complemented them with an extension network of generic vessels in the frontal and occipital lobes to guarantee even overall blood supply to the entire brain volume. An explicit Monte Carlo simulation was implemented to track the propagation of each individual blood particle (BP) through the brain and time-dependent radiation fields, accumulating dose along their trajectories. The cerebral model includes 1050 path lines and explicitly simulates more than 266 000 BP at any given time that are tracked with a time resolution of 10 ms. The entire BFM for the whole body contains 22 178 000 BP, corresponding to 4200 BP per ml of blood. We have used the model to investigate the difference between proton and photon therapy, and the effect of different dose rates and patient characteristics on the dose to the circulating blood pool. The mean dose to the blood pool is estimated to be 0.06 and 0.13 Gy after 30 fractions of proton and photon therapy, respectively, and the highest dose to 1% of blood was found to be 0.19 Gy and 0.34 Gy. The fraction of blood volume receiving any dose after the first fraction is significantly lower for proton therapy, 10.1% compared to 18.4% for the photon treatment plan. 90% of the blood pool will have received dose after the 11th fraction using photon therapy compared to the 21st fraction with proton therapy. Higher dose rates can effectively reduce the fraction of blood irradiated to low doses but increase the amount of blood receiving high doses. Patient characteristics such as blood pressure, gender and age lead to smaller effects than variations in the dose rate. We developed a 4D human BFM including recirculating to estimate the radiation dose to the circulating blood during intracranial treatment and demonstrate its application to proton- versus photon-based delivery, various dose rates and patient characteristics. The radiation dose estimation to the circulating blood provides us better insight into the origins of radiation-induced lymphopenia.

Global Survey of Outcomes of Neurocritical Care Patients: Analysis of the PRINCE Study Part 2.

BACKGROUND: Neurocritical care is devoted to the care of critically ill patients with acute neurological or neurosurgical emergencies. There is limited information regarding epidemiological data, disease characteristics, variability of clinical care, and in-hospital mortality of neurocritically ill patients worldwide. We addressed these issues in the Point PRevalence In Neurocritical CarE (PRINCE) study, a prospective, cross-sectional, observational study. METHODS: We recruited patients from various intensive care units (ICUs) admitted on a pre-specified date, and the investigators recorded specific clinical care activities they performed on the subjects during their first 7 days of admission or discharge (whichever came first) from their ICUs and at hospital discharge. In this manuscript, we analyzed the final data set of the study that included patient admission characteristics, disease type and severity, ICU resources, ICU and hospital length of stay, and in-hospital mortality. We present descriptive statistics to summarize data from the case report form. We tested differences between geographically grouped data using parametric and nonparametric testing as appropriate. We used a multivariable logistic regression model to evaluate factors associated with in-hospital mortality. RESULTS: We analyzed data from 1545 patients admitted to 147 participating sites from 31 countries of which most were from North America (69%, N = 1063). Globally, there was variability in patient characteristics, admission diagnosis, ICU treatment team and resource allocation, and in-hospital mortality. Seventy-three percent of the participating centers were academic, and the most common admitting diagnosis was subarachnoid hemorrhage (13%). The majority of patients were male (59%), a half of whom had at least two comorbidities, and median Glasgow Coma Scale (GCS) of 13. Factors associated with in-hospital mortality included age (OR 1.03; 95% CI, 1.02 to 1.04); lower GCS (OR 1.20; 95% CI, 1.14 to 1.16 for every point reduction in GCS); pupillary reactivity (OR 1.8; 95% CI, 1.09 to 3.23 for bilateral unreactive pupils); admission source (emergency room versus direct admission [OR 2.2; 95% CI, 1.3 to 3.75]; admission from a general ward versus direct admission [OR 5.85; 95% CI, 2.75 to 12.45; and admission from another ICU versus direct admission [OR 3.34; 95% CI, 1.27 to 8.8]); and the absence of a dedicated neurocritical care unit (NCCU) (OR 1.7; 95% CI, 1.04 to 2.47). CONCLUSION: PRINCE is the first study to evaluate care patterns of neurocritical patients worldwide. The data suggest that there is a wide variability in clinical care resources and patient characteristics. Neurological severity of illness and the absence of a dedicated NCCU are independent predictors of in-patient mortality.

First experimental measurement of the effect of cardio-synchronous brain motion on the dose distribution during microbeam radiation therapy.

PURPOSE: Microbeam radiation therapy (MRT) is an emerging radiation oncology modality ideal for treating inoperable brain tumors. MRT employs quasi-parallel beams of low-energy x rays produced from modern synchrotrons. A tungsten carbide multislit collimator (MSC) spatially fractionates the broad beam into rectangular beams. In this study, the MSC creates beams 50 µm wide ("peaks") separated by a center-to-center distance of 400 µm ("valleys"). The peak to valley dose ratio (PVDR) is of critical importance to the efficacy of MRT. The underlying radiobiological advantage of MRT relies on high peak dose for tumor control and low valley dose for healthy tissue sparing. Cardio synchronous brain motion of the order 100-200 µm is comparable to microbeam width and spacing. The motion can have a detrimental effect on the PVDR, full width at half maximum (FWHM) of the microbeams, and ultimately the dose distribution. We present the first experimental measurement of the effect of brain motion on MRT dose distribution. Dosimetry in MRT is difficult due to the high dose rate (up to 15-20 kGy/s) and small field sizes. METHODS: A real-time dosimetry system based on a single silicon strip detector (SSSD) has been developed with spatial resolution ~10 µm. The SSSD was placed in a water-equivalent phantom and scanned through the microbeam distribution. A monodirectional positioning stage reproduced brain motion during the acquisition. Microbeam profiles were reconstructed from the SSSD and compared with Geant4 simulation and radiochromic HD-V2 film. RESULTS: The SSSD is able to reconstruct dose profiles within 2 µm compared to film. When brain motion is applied the SSSD shows a two time increase in FWHM of profiles and 50% reduction in PVDR. This is confirmed by Geant4 and film data. CONCLUSIONS: Motion-induced misalignment and distortion of microbeams at treatment delivery will result in a reduced PVDR and increased irradiation of additional healthy tissue compromising the radiobiological effectiveness of MRT. The SSSD was able to reconstruct dose profiles under motion conditions and predict similar effects on FWHM and PVDR as by the simulation. The SSSD is a simple to setup, real-time detector which can provide time-resolved high spatial resolution dosimetry of microbeams in MRT.

Determination of optimal time window for cortical mapping in awake craniotomy: assessment of intraoperative reaction speed.

Currently, there is no known time frame when the patients are the most responsive during awake craniotomy. The aim of this work is therefore to determine when the patient has the shortest reaction time and so to extrapolate the optimal time window for cortical mapping. In this analytic observational study, our group has recorded the reaction times of 35 patients undergoing an awake craniotomy and compared them with the preoperative baseline. The operations were performed according to a "sleep-awake-awake" protocol. Data collection was performed in parallel with standard methods for evaluation of language and cognitive functions. The preoperative reaction times of our patient cohort (average ± SD = 510 ± 124 ms) were significantly shorter than those measured during the operation 786 ± 280 ms, p < .001. A one-factor ANOVA within subjects showed a significant increase in reaction times; p < .001. Post hoc comparisons on a Bonferroni-corrected α-error level of .05 showed significant differences between the reaction speed during the 0-10 min time frame and the preoperative baseline, as well as the intraoperative reaction times during the 20-30 min, 30-40 min, and the t > 40 min time frames. In conclusion, measurement of intraoperative reaction speed seems to be a technically feasible method that is well tolerated by the patients. The intraoperative reaction speed performance was shown to be significantly slower than on the day before the operation. The patients seem to be the slowest directly after extubation and gradually wake up during the awake phase. The poorest wakefulness is demonstrated during the first 20 min after extubation.

Quantitative Assessment of Tumor Cell Proliferation in Brain Gliomas with Dynamic Contrast-Enhanced MRI.

RATIONALE AND OBJECTIVES: This study aimed to investigate whether volume transfer constant (Ktrans) and volume of extravascular extracellular space per unit volume of tissue (Ve) derived from dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) could quantitatively assess the tumor proliferation index (Ki-67) of gliomas noninvasively. MATERIALS AND METHODS: The preoperative DCE MRI data of 69 patients with pathologically confirmed glioma (28, 8, and 33 cases in grades Ⅱ, Ⅲ, and Ⅳ) were retrospectively reviewed. The maximal Ktrans and Ve were measured in the tumor body. The immunohistochemistry was used to detect the expression of Ki-67 proteins in glioma specimens. The Mann-Whitney U test was applied to analyze the differences in Ktrans, Ve, and Ki-67 index across histologically defined glioma grades. Spearman correlation was performed between Ktrans, Ve, and Ki-67 index. The receiver operating characteristic curve analysis was used to determine the cutoff values of Ktrans and Ve in distinguishing different Ki-67 index expression levels. RESULTS: Ktrans, Ve, and Ki-67 index of grade Ⅱ (0.027 min-1, 0.065, 4.04%) were significantly lower than those of grade Ⅲ (0.093 min-1, 0.297, 25.13%) and Ⅳ (0.100 min-1, 0.299, 25.37%). Both Ktrans and Ve significantly correlated with the Ki-67 index in all tumors and high-grade gliomas (HGGs, grade Ⅲ and Ⅳ). The receiver operating characteristic curve analysis revealed that the cutoff values for Ktrans (0.079 min-1) and Ve (0.249) provided the best combination of sensitivity and specificity to distinguish the gliomas with high Ki-67 index from those with low Ki-67 index. CONCLUSION: The DCE MRI-derived parameters were valuable in assessing the tumor cell proliferation in HGG noninvasively.

Holistic needs assessment in brain cancer patients: A systematic review of available tools.

This systematic review describes tools which could be considered for use for holistic needs assessment (HNA) in brain cancer. MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PsycINFO were searched. Studies were included which met the following criteria; primary research published in English which reported the development, psychometric testing or clinical utility testing of patient-reported outcome measures (PROMs) for the assessment of adult brain cancer patients' needs, problems or concerns or generic cancer needs assessment tools developed specifically on a brain cancer or brain tumour population. Nine articles describing four tools were identified. The tools were first assessed using the COSMIN protocol for systematic reviews of measurement properties and then assessed for their quality and usefulness as a holistic needs assessment tool. None of the four tools had strong psychometric properties; however, the two symptom questionnaires had better psychometric properties but would need adapted to holistically assess the multiple domains of need. The two HNA tools had only minimal psychometric testing. The lack of a tool, which adequately meets all requirements for HNA, supports the need to further development of tools to optimise this intervention.

Tumor-related epilepsy: epidemiology, pathogenesis and management.

INTRODUCTION: Seizure is a common comorbidity in patients with brain tumor. It may be the presenting symptom or develop after the tumor diagnosis. The underlying pathophysiology of brain tumor-related epilepsy remains poorly understood. METHODS: A comprehensive literature review of Pubmed English articles from 1980-2017 was performed to summarize current knowledge and treatment options of brain tumor-related epilepsy. RESULTS: Multiple factors have been found to contribute to tumor-related epilepsy, including tumor type, speed of tumor growth, location, and tumor burden. The underlying pathogenesis of epilepsy is not clear but perturbations in the peri-tumoral regions, both structural and cellular communications, have been implicated. CONCLUSIONS: Surgical and medical treatments of tumor-related epilepsy remain challenging as additional factors such as the extent of surgical resection, interactions with tumor-related oncological treatments and anti-epileptic medication related side effects need to be considered.

Assessment of the praxis circuit in glioma surgery to reduce the incidence of postoperative and long-term apraxia: a new intraoperative test.

OBJECTIVEApraxia is a cognitive-motor deficit affecting the execution of skilled movements, termed praxis gestures, in the absence of primary sensory or motor disorders. In patients affected by stroke, apraxia is associated with lesions of the lateral parietofrontal stream, connecting the posterior parietal areas with the ventrolateral premotor area and subserving sensory-motor integration for the hand movements. In the neurosurgical literature to date, there are few reports regarding the incidence of apraxia after glioma surgery. A retrospective analysis of patients who harbored a glioma around the central sulcus and close to the parietofrontal circuits in depth showed a high incidence of long-term postoperative hand apraxia, impairing the patients' quality of life. To avoid the occurrence of postoperative apraxia, the authors sought to develop an innovative intraoperative hand manipulation task (HMt) that can be used in association with the brain mapping technique to identify and preserve the cortical and subcortical structures belonging to the praxis network.METHODSThe intraoperative efficacy of the HMt was investigated by comparing the incidence of postoperative ideomotor apraxia between patients undergoing mapping with (n = 79) and without (n = 41) the HMt. Patient groups were balanced for all demographic and clinical features.RESULTSIn patients with lesions in the dominant hemisphere, the HMt dramatically reduced the incidence of apraxia, with a higher sensitivity for the ideomotor than for the constructional abilities; patients with lesions in the nondominant hemisphere benefitted from the HMt for both ideomotor and constructional abilities. The administration of the test did not reduce the extent of resection.CONCLUSIONSThe HMt is a safe and feasible intraoperative tool that allowed surgeons to prevent the occurrence of long-term hand apraxia while attaining resection goals for the surgical treatment of glioma.

Brain metastases in non-small cell lung cancer patients on epidermal growth factor receptor tyrosine kinase inhibitors: symptom and economic burden.

OBJECTIVE: This study describes the symptom and economic burden associated with brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) receiving epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs). METHODS: This retrospective study included adults with ≥2 medical claims, within 90 days, for lung cancer and ≥1 administration of EGFR-TKIs. Based on ICD-9 codes, patients were stratified into cohorts by type of metastases (BM, other metastases [OM], or no metastases [NM]), and by when the metastasis diagnosis occurred (synchronous or asynchronous). RESULTS: The population (synchronous BM [SBM] = 24, synchronous OM [SOM] = 23, asynchronous BM [ASBM] = 15, asynchronous OM [ASOM] = 49, NM = 85) was mostly female (57%), average age 69 years (SD = 11). SBM patients experienced more fatigue and nausea/vomiting compared with SOM and NM patients and more headaches and loss of appetite than NM patients. ASBM was associated with more fatigue, nausea/vomiting, headaches, pain/numbness, altered mental status, and seizures than NM, and more headaches and pain/numbness than ASOM. SBM patients experienced a greater increase in per-member-per-month all-cause total healthcare costs after diagnosis ($20,301) vs SOM ($9,131, p = .001) and NM ($2,493, p = .001). ASBM's cost increase between baseline and follow-up ($7,867) did not differ from ASOM's ($4,947, p = .195); both were larger than NM ($2,493, p = .001 and p = .009, respectively). LIMITATIONS: EGFR mutation status was inferred based on EGFR-TKI treatment, not by molecular testing. Patients were from US commercial insurance plans; results may not be generalizable to other populations. CONCLUSIONS: Among patients with EGFR-TKI-treated NSCLC, patients with BM experienced more symptoms and, when diagnosed synchronously, had significant increases in total medical costs vs patients with OM and NM. Therapeutic options with central nervous system activity may offer advantages in symptomatology and costs in EGFR-mutated patients with BM.

Value of Frequency Domain Resting-State Functional Magnetic Resonance Imaging Metrics Amplitude of Low-Frequency Fluctuation and Fractional Amplitude of Low-Frequency Fluctuation in the Assessment of Brain Tumor-Induced Neurovascular Uncoupling.

The aim of this study was to explore whether the phenomenon of brain tumor-related neurovascular uncoupling (NVU) in resting-state blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) (rsfMRI) may also affect the resting-state fMRI (rsfMRI) frequency domain metrics the amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). Twelve de novo brain tumor patients, who underwent clinical fMRI examinations, including task-based fMRI (tbfMRI) and rsfMRI, were included in this Institutional Review Board-approved study. Each patient displayed decreased/absent tbfMRI activation in the primary ipsilesional (IL) sensorimotor cortex in the absence of a corresponding motor deficit or suboptimal task performance, consistent with NVU. Z-score maps for the motor tasks were obtained from general linear model analysis (reflecting motor activation vs. rest). Seed-based correlation analysis (SCA) maps of sensorimotor network, ALFF, and fALFF were calculated from rsfMRI data. Precentral and postcentral gyri in contralesional (CL) and IL hemispheres were parcellated using an automated anatomical labeling template for each patient. Region of interest (ROI) analysis was performed on four maps: tbfMRI, SCA, ALFF, and fALFF. Voxel values in the CL and IL ROIs of each map were divided by the corresponding global mean of ALFF and fALFF in the cortical brain tissue. Group analysis revealed significantly decreased IL ALFF (p = 0.02) and fALFF (p = 0.03) metrics compared with CL ROIs, consistent with similar findings of significantly decreased IL BOLD signal for tbfMRI (p = 0.0005) and SCA maps (p = 0.0004). The frequency domain metrics ALFF and fALFF may be markers of lesion-induced NVU in rsfMRI similar to previously reported alterations in tbfMRI activation and SCA-derived resting-state functional connectivity maps.

Peri- and intraoperative cognitive and language assessment for surgical resection in brain eloquent structures.

Neuropsychological care of patients suffering from an infiltrative glioma and candidates for a neurosurgery under awake condition with intraoperative functional mapping is a critical and mandatory stage in therapeutic management. It enables to estimate the functional impact of the tumor and, consequently, the efficacy of functional reorganization typically observed in these patients, not only to better predict surgery outcomes and select appropriate tasks for intraoperative functional mapping, but also to plan efficient and individualized postoperative cognitive rehabilitation strategies. Neuropsychological care management also enables patients to benefit from a solid psychological preparation both to the surgery and its associated transitory functional consequences, as well as provide a personalized psychological and emotional long-term support. Based on their solid experience in the peri-operative care of diffuse low-grade glioma patients, the authors thoroughly describe the different stages of neuropsychological management. Cognitive, emotional and language assessments typically used by the authors around and during surgery are reported, and different possible avenues of improvement are further discussed.

Pseudoprogression, radionecrosis, inflammation or true tumor progression? challenges associated with glioblastoma response assessment in an evolving therapeutic landscape.

The wide variety of treatment options that exist for glioblastoma, including surgery, ionizing radiation, anti-neoplastic chemotherapies, anti-angiogenic therapies, and active or passive immunotherapies, all may alter aspects of vascular permeability within the tumor and/or normal parenchyma. These alterations manifest as changes in the degree of contrast enhancement or T2-weighted signal hyperintensity on standard anatomic MRI scans, posing a potential challenge for accurate radiographic response assessment for identifying anti-tumor effects. The current review highlights the challenges that remain in differentiating true disease progression from changes due to radiation therapy, including pseudoprogression and radionecrosis, as well as immune or inflammatory changes that may occur as either an undesired result of cytotoxic therapy or as a desired consequence of immunotherapies.

Assessment of Cognitive, Emotional, and Motor Domains in Patients with Diffuse Gliomas Using the National Institutes of Health Toolbox Battery.

OBJECTIVE: Patients with brain tumors are known to have deficits in cognitive, motor, and emotional domains. Comprehensive evaluation of the patient with brain tumor includes taking into account all these domains at baseline and throughout treatment. Standard neuropsychological assessment methods, however, are lengthy, expensive, and often are variable. The authors appraised the feasibility of using a brief, inexpensive, comprehensive, and standardized neuropsychological battery, the National Institutes of Health (NIH) Toolbox, to assess these domains in patients with diffuse glioma. METHODS: Eighteen patients were recruited and completed the NIH Toolbox Cognitive Battery, 2 motor tests (Grip Strength and Grooved Pegboard), and the NIH Toolbox Emotional Battery. Fully corrected T scores are reported, as well as composite scores of fluid and crystallized cognition. Follow-up cognitive (n = 13) and motor assessment (n = 12) were performed at 1 month after surgery. RESULTS: The total time to complete the battery was approximately 60 minutes. A total of 78% of patients demonstrated significant impairment on one or more cognitive test, whereas 37% had impaired fluid cognition. Crystallized and overall composite cognitive scores were relatively intact, with 16% of patients showing significant impairment. A total of 22% of patients had impaired strength in the left hand, and 22% had impaired dexterity in both hands. In addition, 50% of patients showed impairment in one or more emotional domain. At 1 month after surgery, a significant decrease in crystallized cognition was observed. CONCLUSIONS: The NIH Toolbox represents a feasible alternative to current neuropsychological batteries in the assessment of neurosurgical patients. It can be administered quickly, inexpensively, and will give the neurosurgical community a common currency when reporting neuropsychological results.

High resolution CBV assessment with PEAK-EPI: k-t-undersampling and reconstruction in echo planar imaging.

PURPOSE: Achieving higher spatial resolution and improved brain coverage while mitigating in-plane susceptibility artifacts in the assessment of perfusion parameters, such as cerebral blood volume, in echo planar imaging (EPI)-based dynamic susceptibility contrast weighted cerebral perfusion measurements. METHODS: PEAK-EPI, an EPI sequence with interleaved readout trajectories and three different strategies for autocalibration-signal acquisition (inplace, dynamic extra and extra) is presented. Performance of each approach is analyzed in vivo based on flip angle variation induced dynamics, assessing temporal fidelity, temporal SNR and g-factors. All approaches are compared with conventional GRAPPA reconstructions. PEAK-EPI with inplace autocalibration-signal at R = 5 is then compared with the standard clinical EPI protocol in six patients, using two half-dose dynamic susceptibility contrast weighted cerebral perfusion measurements per subject. RESULTS: PEAK-EPI acquisition facilitates a substantial increase of spatial resolution at a higher number of slices per TR and provides improved SNR compared to conventional GRAPPA. High dependency of the resulting reconstruction quality on the type of autocalibration-signal acquisition is observed. PEAK-EPI with inplace autocalibration-signal achieves high temporal fidelity and initial feasibility is shown. CONCLUSION: The obtained high resolution cerebral blood volume maps reveal more detailed information than in corresponding standard EPI measurements and facilitate detailed delineation of tumorous tissue. Magn Reson Med 77:2153-2166, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Simultaneous assessment of cerebral blood volume and diffusion heterogeneity using hybrid IVIM and DK MR imaging: initial experience with brain tumors.

OBJECTIVES: To investigate the feasibility of simultaneously assessing cerebral blood volume and diffusion heterogeneity using hybrid diffusion-kurtosis (DK) and intravoxel-incoherent-motion (IVIM) MR imaging. METHODS: Fifteen healthy volunteers and 30 patients with histologically proven brain tumours (25 WHO grade II-IV gliomas and five metastases) were recruited. On a 3-T system, diffusion-weighted imaging was performed with six b-values ranging from 0 to 1,700 s/mm2. Nonlinear least-squares fitting was employed to extract diffusion coefficient (D), diffusion kurtosis coefficient (K, a measure of the degree of non-Gaussian and heterogeneous diffusion) and intravascular volume fraction (f, a measure proportional to cerebral blood volume). Repeated-measures multivariate analysis of variance and receiver operating characteristic analysis were performed to assess the ability of D/K/f in differentiating contrast-enhanced tumour from peritumoral oedema and normal-appearing white matter. RESULTS: Based on our imaging setting (baseline signal-to-noise ratio = 32-128), coefficient of variation was 14-20 % for K, ~6 % for D and 26-44 % for f. The indexes were able to differentiate contrast-enhanced tumour (Wilks' λ = 0.026, p < 10-3), and performance was greatest with K, followed by f and D. CONCLUSIONS: Hybrid DK IVIM imaging is capable of simultaneously measuring cerebral perfusion and diffusion indexes that together may improve brain tumour diagnosis. KEY POINTS: • Hybrid DK-IVIM imaging allows simultaneous measurement of K, D and f. • Combined K/D/f better demarcates contrast-enhanced tumour than they do separately. • f correlates better with contrast-leakage-corrected CBV DSC than with uncorrected CBV DSC.

The sensory-motor profile awake-A new tool for pre-, intra-, and postoperative assessment of sensory-motor function.

OBJECTIVES: Awake craniotomy is a well-established procedure in surgery of intracranial tumors in eloquent areas. However, sufficiently standardized instruments for the assessment of sensory-motor function before, during and after the operation are currently lacking, despite their importance for evaluation of operative outcome. PATIENTS AND METHODS: To address this issue, we designed a standardized assessment tool (the "sensory-motor profile awake scale"; SMP-a). The final scale consists of three motor sections (face, arm and leg) assessing both gross and fine motor skills and one sensory section. It differentiates between six grades of impairment and its tasks are applicable for intraoperative continuous monitoring of sensory-motor functions and supporting processes. We analyzed the data of 17 patients with intracranial tumors eligible for awake craniotomy who were preoperatively assessed with the SMP-a. In addition, we present an exemplary case. RESULTS: Our data support the assumption that the SMP-a is feasible in patients eligible for awake craniotomy, even in patients with symptoms of mild aphasia or more severe sensory-motor deficits caused by tumor recurrence. The exemplary case demonstrates the feasibility of repeated measures with the SMP-a in a tumor patient, including the adaption of tasks to the individual requirements of an intraoperative setting. CONCLUSION: This exploratory study suggests that the SMP-a might be a feasible rating scale in patients with intracranial tumors. The flexibility of the scale enables individual adaption, but preserves the standardized scoring system to allow comparison between assessment dates, patients and, hopefully in the future, institutions. However, future studies are mandatory to provide data on the instrument's diagnostic properties with respect to feasibility, objectivity, validity and reliability.

Photon spectrum and absorbed dose in brain tumor.

Using Monte Carlo methods a BOMAB phantom inside a treatment hall with a brain tumor nearby the pituitary gland was treated with photons produced by a Varian 6MV linac. The photon spectrum and the absorbed dose were calculated in the tumor, pituitary gland and the head. The treatment beam was collimated to illuminate only the tumor volume; however photons were noticed in the gland. Photon fluence reaching the tumor is and 15.7 times larger than the fluence in the pituitary gland, on the other hand the absorbed dose in the tumor is 37.1 times larger than the dose in the gland because photons that reach the pituitary gland are scattered, by the head and the tumor, through Compton effect.

Presurgical Assessment of the Sensorimotor Cortex Using Resting-State fMRI.

BACKGROUND AND PURPOSE: The functional characterization of the motor cortex is an important issue in the presurgical evaluation of brain lesions. fMRI noninvasively identifies motor areas while patients are asked to move different body parts. This task-based approach has some drawbacks in clinical settings: long scanning times and exclusion of patients with severe functional or neurologic disabilities and children. Resting-state fMRI can avoid these difficulties because patients do not perform any goal-directed tasks. MATERIALS AND METHODS: Nineteen patients with diverse brain pathologies were prospectively evaluated by using task-based and resting-state fMRI to localize sensorimotor function. Independent component analyses were performed to generate spatial independent components reflecting functional brain networks or noise. Three radiologists identified the motor components and 3 portions of the motor cortex corresponding to the hand, foot, and face representations. Selected motor independent components were compared with task-based fMRI activation maps resulting from movements of the corresponding body parts. RESULTS: The motor cortex was successfully and consistently identified by using resting-state fMRI by the 3 radiologists for all patients. When they subdivided the motor cortex into 3 segments, the sensitivities of resting-state and task-based fMRI were comparable. Moreover, we report a good spatial correspondence with the task-based fMRI activity estimates. CONCLUSIONS: Resting-state fMRI can reliably image sensorimotor function in a clinical preoperative routine. It is a promising opportunity for presurgical localization of sensorimotor function and has the potential to benefit a large number of patients affected by a wide range of pathologies.

The Last 10 Days of Patients With Glioblastoma: Assessment of Clinical Signs and Symptoms as well as Treatment.

BACKGROUND: High-grade gliomas are the most frequent primary brain tumors. Despite improvement in diagnostics and treatment, survival is still poor and quality-of-life issues are of major importance. Little is known regarding the clinical signs and symptoms of dying patients with glioblastoma. OBJECTIVE: The aim of this study was to investigate signs and symptoms as well as therapeutic strategies in patients with glioblastoma in the end-of-life phase in order to improve end-of-life care. METHODS: In this prospective single-center study, clinical data were obtained using a standardized protocol. We descriptively analyzed signs, symptoms, and therapeutic strategies on a daily basis. RESULTS: A total of 57 patients, who died due to glioblastoma in a hospital setting, were included. The most frequent signs and symptoms in the last 10 days before death were decrease in level of consciousness (95%), fever (88%), dysphagia (65%), seizures (65%), and headache (33%). Concerning medication, 95% received opioids. There was a high need for nonsteroidal anti-inflammatory drugs (77%) and anticonvulsants (75%). Steroids were given to 56%. CONCLUSION: Due to a decrease in level of consciousness and cognitive impairment, assessment of clinical signs and symptoms such as headache at the end of life is difficult. Based on the signs and symptoms in the last days before death in patients with glioblastoma, supportive drug treatment remains challenging. Our study emphasizes the importance of standardized guidelines for end-of-life care in patients with glioblastoma.