An Open-Source Tool for Anisotropic Radiation Therapy Planning in Neuro-oncology Using DW-MRI Tractography.

There is evidence from histopathological studies that glioma tumor cells migrate preferentially along large white matter bundles. If the peritumoral white matter structures can be used to predict the likely trajectory of migrating tumor cells outside of the surgical margin, then this information could be used to inform the delineation of radiation therapy (RT) targets. In theory, an anisotropic expansion that takes large white matter bundle anatomy into account may maximize the chances of treating migrating cancer cells and minimize the amount of brain tissue exposed to high doses of ionizing radiation. Diffusion-weighted MRI (DW-MRI) can be used in combination with fiber tracking algorithms to model the trajectory of large white matter pathways using the direction and magnitude of water movement in tissue. The method presented here is a tool for translating a DW-MRI fiber tracking (tractography) dataset into a white matter path length (WMPL) map that assigns each voxel the shortest distance along a streamline back to a specified region of interest (ROI). We present an open-source WMPL tool, implemented in the package Diffusion Imaging in Python (DIPY), and code to convert the resulting WMPL map to anisotropic contours for RT in a commercial treatment planning system. This proof-of-concept lays the groundwork for future studies to evaluate the clinical value of incorporating tractography modeling into treatment planning

Comparison of progression of diffuse axonal injury with histology and diffusion tensor imaging

Diffuse axonal injury, also known as traumatic axonal injury (TAI), is a major contributor to the pathology of traumatic brain injury. However, TAI is undetectable to conventional clinical magnetic resonance (MR) imaging techniques. Histologically, TAI is characterized by swollen axons that eventually disconnect and form axonal retraction balls (RB) in various white matter tracts. MR-diffusion tensor imaging (MR-DTI) has been reported to be sensitive to TAI in human TBI patients by measuring water molecular diffusion motion in white matter fiber tracts. To date, only one correlative animal study has been carried out to investigate the DTI relationship to TAI, and it has reported a relationship between DTI changes and TAI. No other animal study has validated the correlation between DTI and TAI. Therefore, this study is the second animal study that has examinedthe correlation between histological observations of axonal damage in white mater tract and the DTI measurements over time. TAI was induced in twenty-four anaesthetized male Sprague Dawley rats utilizing an impact acceleration device (Marmarou et al 1994). T2 weighted MR images, and DTI images were acquired in vivo pre-impact, and four hours, twenty-four hours, three days and seven days post-impact. The DTI images were obtained in a Bruker 4.7 Tesla scanner in six gradient directions. Fractional anisotropy (FA), diffusion trace, axial diffusivity (AD) and radial diffusivity (RD) were calculated by using DTI Studio (Johns Hopkins University). After imaging, perfused brain tissue was processed for &beta-amyloid precursor protein (&beta-APP) and RMO14 immunocytochemistry and quantified by ImageJ software (NIH) for each time point. &beta-APP and RMO14 immunoreactive axons were observed in optic chiasm (Och) and corpus callosum (CC). TAI was more prevalent and less variable in the Och in comparison to CC. In the Och and CC &beta-APP positive axons were more prominent at eight hours and twenty-eight hours post-TBI and decreased as time elapsed. In the Och and CC RMO14 positive axons were more prominent at twenty-eight hours post-TBI and decreased as time elapsed. However, at seven days post-TBI a modest increase of RMO14 positive axons occurred in comparison to three days post TBI. The mean FA values of the DTI image of the Och and CC revealed a decrease of FA at four hours post-TBI (p\u3c0.05). After four hours post-TBI the FA value increased and remained increased up to seven days post-TBI in the CC and Och. The other DTI parameters also changed over time. No linear relationship was found between FA and TAI density and between AD and TAI density in the CC and Och. The diffusion trace was found to be correlated with TAI density at four hours and seven day post-TBI in the Och and CC respectively. The RD was found to be correlated with TAI density at four hours and seven days post-TBI in the Och. This study was unable to verify that the DTI changes after TBI are an indication of TAI. However, the DTI parameters did change as time elapsed after TBI. The profile of the DTI parameter changes may be an indication of edema. In addition, other imaging parameters, diffusion trace and RD, did show correlation with the density &beta-APP positive axons and may be the better DTI parameters for describing axonal integrity such as axonal permeability

Magnetic Resonance Imaging of Gliomas

Open Access.This work was supported in part by grants CTQ2010-20960-C02-02 to P.L.L. and grant SAF2008-01327 to S.C. A.M.M. held an Erasmus Fellowship from Coimbra University and E.C.C. a predoctoral CSIC contract.Peer Reviewe

Effects of Multi-Shell Free Water Correction on Glioma Characterization.

Diffusion MRI is a useful tool to investigate the microstructure of brain tumors. However, the presence of fast diffusing isotropic signals originating from non-restricted edematous fluids, within and surrounding tumors, may obscure estimation of the underlying tissue characteristics, complicating the radiological interpretation and quantitative evaluation of diffusion MRI. A multi-shell regularized free water (FW) elimination model was therefore applied to separate free water from tissue-related diffusion components from the diffusion MRI of 26 treatment-naïve glioma patients. We then investigated the diagnostic value of the derived measures of FW maps as well as FW-corrected tensor-derived maps of fractional anisotropy (FA). Presumed necrotic tumor regions display greater mean and variance of FW content than other parts of the tumor. On average, the area under the receiver operating characteristic (ROC) for the classification of necrotic and enhancing tumor volumes increased by 5% in corrected data compared to non-corrected data. FW elimination shifts the FA distribution in non-enhancing tumor parts toward higher values and significantly increases its entropy (p ≤ 0.003), whereas skewness is decreased (p ≤ 0.004). Kurtosis is significantly decreased (p < 0.001) in high-grade tumors. In conclusion, eliminating FW contributions improved quantitative estimations of FA, which helps to disentangle the cancer heterogeneity

Effects of Multi-Shell Free Water Correction on Glioma Characterization.

Diffusion MRI is a useful tool to investigate the microstructure of brain tumors. However, the presence of fast diffusing isotropic signals originating from non-restricted edematous fluids, within and surrounding tumors, may obscure estimation of the underlying tissue characteristics, complicating the radiological interpretation and quantitative evaluation of diffusion MRI. A multi-shell regularized free water (FW) elimination model was therefore applied to separate free water from tissue-related diffusion components from the diffusion MRI of 26 treatment-naïve glioma patients. We then investigated the diagnostic value of the derived measures of FW maps as well as FW-corrected tensor-derived maps of fractional anisotropy (FA). Presumed necrotic tumor regions display greater mean and variance of FW content than other parts of the tumor. On average, the area under the receiver operating characteristic (ROC) for the classification of necrotic and enhancing tumor volumes increased by 5% in corrected data compared to non-corrected data. FW elimination shifts the FA distribution in non-enhancing tumor parts toward higher values and significantly increases its entropy (p ≤ 0.003), whereas skewness is decreased (p ≤ 0.004). Kurtosis is significantly decreased (p < 0.001) in high-grade tumors. In conclusion, eliminating FW contributions improved quantitative estimations of FA, which helps to disentangle the cancer heterogeneity

Tumor Tissue Detection using Blood-Oxygen-Level-Dependent Functional MRI based on Independent Component Analysis

Accurate delineation of gliomas from the surrounding normal brain areas helps maximize tumor resection and improves outcome. Blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) has been routinely adopted for presurgical mapping of the surrounding functional areas. For completely utilizing such imaging data, here we show the feasibility of using presurgical fMRI for tumor delineation. In particular, we introduce a novel method dedicated to tumor detection based on independent component analysis (ICA) of resting-state fMRI (rs-fMRI) with automatic tumor component identification. Multi-center rs-fMRI data of 32 glioma patients from three centers, plus the additional proof-of-concept data of 28 patients from the fourth center with non-brain musculoskeletal tumors, are fed into individual ICA with different total number of components (TNCs). The best-fitted tumor-related components derived from the optimized TNCs setting are automatically determined based on a new template-matching algorithm. The success rates are 100%, 100% and 93.75% for glioma tissue detection for the three centers, respectively, and 85.19% for musculoskeletal tumor detection. We propose that the high success rate could come from the previously overlooked ability of BOLD rs-fMRI in characterizing the abnormal vascularization, vasomotion and perfusion caused by tumors. Our findings suggest an additional usage of the rs-fMRI for comprehensive presurgical assessment

An examination of the temporal and spatial evolution of a small permanent focal ischemic lesion

The research reported here was designed to validate our hypothesis that noninvasive imaging could delineate the evolution of a small ischemic infarct. Furthermore, the alterations observed by MR were correlated to histological and inflammatory markers. Finally, intervention with a calcium buffering agent was hypothesized to prevent many of these changes. The first part of this study investigated the development of a small focal cortical lesion produced as a result of a cortical devascularization injury. Diffusion-weighted images (DWI) were collected before injury and at 12, 24, 48 hours and 3, 5, 7 and 14 days after injury and apparent diffusion coefficient (ADC) maps were calculated from the DW images to quantify lesion development. As a second measure of injury, tissue morphology was analyzed using cresyl violet histochemistry. Results indicated a significant reduction in ADC values within the lesion cortex that first appeared at 12 hours after injury and then recovered to control levels by 14 days. ADC changes were also observed in the contralateral cortex. This type of injury also resulted in the progressive but relatively slow formation of a pannecrotic infarct. Both astrocyte and microglia activation occurred early and were present in both hemispheres, however inflammatory cell infiltration was delayed until 48 hours after the injury. Many of these inflammatory cells were tumor necrosis factor a (TNF-a) and interferon y (IFN-y) immunoreactive. Overall, the quantitative and histological measures of this lesion were consistent with those observed in ischemic injury. Moreover, we found DWI to be a sensitive measure of damage associated with a cortical devascularization injury. The second part of this study used 2-aminophenol-N, N, O-triacetic acid acetoxymethyl ester (APTRA-AM) to determine the effectiveness of a calcium buffer in providing neuroprotection after a cortical devascularization injury. Animals were given two intravenous injections of either saline, DMSO, or APTRA-AM at 1 and 12 hours after injury. Animals were then imaged using a multiple b-value DWI sequence prior to injury and then at 12, 24,48 hours, 3 and 7 days after injury. After 7 days the animals were sacrificed and correlative histological and immunocytochemical studies were done. Our results indicate that saline injection after injury resulted in a decrease in the ADC of the lesion cortex within the first 12 hours of injury, which then slowly returned to prescan levels. In contrast, the injection of either DMSO or APTRA-AM after injury resulted in no significant changes in the ADC within the lesion area. Histologically, both saline and DMSO injected animals had pan-necrotic infarcts with concomitant glial activation and inflammatory cell infiltration. APTRA-AM treated animals showed an 86% reduction in lesion area and no evidence of inflammatory cell infiltration. The results presented here clearly demonstrate the effectiveness of APTRA-AM in preventing neuronal cell death and the accompanying inflammatory response when administered post-injury, suggesting that this molecule may be an excellent candidate for future clinical neuroprotection studies