Effect of disease-modifying therapies on subcortical gray matter atrophy in multiple sclerosis.

BACKGROUND: The effects of disease-modifying therapies (DMTs) on region-specific brain atrophy in multiple sclerosis (MS) are unclear. OBJECTIVE: To determine the effects of higher versus lower efficacy DMTs on rates of brain substructure atrophy in MS. METHODS: A non-randomized, observational cohort of people with MS followed with annual brain magnetic resonance imaging (MRI) was evaluated retrospectively. Whole brain, subcortical gray matter (GM), cortical GM, and cerebral white matter (WM) volume fractions were obtained. DMTs were categorized as higher (DMT-H: natalizumab and rituximab) or lower (DMT-L: interferon-beta and glatiramer acetate) efficacy. Follow-up epochs were analyzed if participants had been on a DMT for ⩾6 months prior to baseline and had at least one follow-up MRI while on DMTs in the same category. RESULTS: A total of 86 DMT epochs (DMT-H: n = 32; DMT-L: n = 54) from 78 participants fulfilled the study inclusion criteria. Mean follow-up was 2.4 years. Annualized rates of thalamic (-0.15% vs -0.81%; p = 0.001) and putaminal (-0.27% vs -0.73%; p = 0.001) atrophy were slower during DMT-H compared to DMT-L epochs. These results remained significant in multivariate analyses including demographics, clinical characteristics, and T2 lesion volume. CONCLUSION: DMT-H treatment may be associated with slower rates of subcortical GM atrophy, especially of the thalamus and putamen. Thalamic and putaminal volumes are promising imaging biomarkers in MS.

Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study.

On average, African Americans with multiple sclerosis demonstrate higher inflammatory disease activity, faster disability accumulation, greater visual dysfunction, more pronounced brain tissue damage and higher lesion volume loads compared to Caucasian Americans with multiple sclerosis. Neurodegeneration is an important component of multiple sclerosis, which in part accounts for the clinical heterogeneity of the disease. Brain atrophy appears to be widespread, although it is becoming increasingly recognized that regional substructure atrophy may be of greater clinical relevance. Patient race (within the limitations of self-identified ancestry) is regarded as an important contributing factor. However, there is a paucity of studies examining differences in neurodegeneration and brain substructure volumes over time in African Americans relative to Caucasian American patients. Optical coherence tomography is a non-invasive and reliable tool for measuring structural retinal changes. Recent studies support its utility for tracking neurodegeneration and disease progression in vivo in multiple sclerosis. Relative to Caucasian Americans, African American patients have been found to have greater retinal structural injury in the inner retinal layers. Increased thickness of the inner nuclear layer and the presence of microcystoid macular pathology at baseline predict clinical and radiological inflammatory activity, although whether race plays a role in these changes has not been investigated. Similarly, assessment of outer retinal changes according to race in multiple sclerosis remains incompletely characterized. Twenty-two African Americans and 60 matched Caucasian Americans with multiple sclerosis were evaluated with brain MRI, and 116 African Americans and 116 matched Caucasian Americans with multiple sclerosis were monitored with optical coherence tomography over a mean duration of 4.5 years. Mixed-effects linear regression models were used in statistical analyses. Grey matter (-0.9%/year versus -0.5%: P =0.02), white matter (-0.7%/year versus -0.3%: P =0.04) and nuclear thalamic (-1.5%/year versus -0.7%/year: P =0.02) atrophy rates were approximately twice as fast in African Americans. African Americans also exhibited higher proportions of microcystoid macular pathology (12.1% versus 0.9%, P =0.001). Retinal nerve fibre layer (-1.1% versus -0.8%: P =0.02) and ganglion cell+ inner plexiform layer (-0.7%/year versus -0.4%/year: P =0.01) atrophy rates were faster in African versus Caucasian Americans. African Americans on average exhibited more rapid neurodegeneration than Caucasian Americans and had significantly faster brain and retinal tissue loss. These results corroborate the more rapid clinical progression reported to occur, in general, in African Americans with multiple sclerosis and support the need for future studies involving African Americans in order to identify individual differences in treatment responses in multiple sclerosis.

Thalamus segmentation using multi-modal feature classification: Validation and pilot study of an age-matched cohort.

Automatic segmentation of the thalamus can be used to measure differences and track changes in thalamic volume that may occur due to disease, injury or normal aging. An automatic thalamus segmentation algorithm incorporating features from diffusion tensor imaging (DTI) and thalamus priors constructed from multiple atlases is proposed. Multiple atlases with corresponding manual thalamus segmentations are registered to the target image and averaged to generate the thalamus prior. At each voxel in a region of interest around the thalamus, a multidimensional feature vector that includes the thalamus prior as well as a set of DTI features, including fractional anisotropy, mean diffusivity, and fiber orientation is formed. A random forest is trained to classify each voxel as belonging to the thalamus or background within the region of interest. Using a leave-one-out cross-validation on nine subjects, the proposed algorithm achieves a mean Dice score of 0.878 and 0.890 for the left and right thalami, respectively, which are higher Dice scores than the three state-of-art methods we compared to. We demonstrate the utility of the method with a pilot study exploring the difference in the thalamus fraction between 21 multiple sclerosis (MS) patients and 21 age-matched healthy controls. The left and right thalamic volumes (normalized by intracranial volumes) are larger in healthy controls by 7.6% and 7.3% respectively, compared to MS patients (though neither result is statistically significant).

Correlated diffusion imaging.

BACKGROUND: Prostate cancer is one of the leading causes of cancer death in the male population. Fortunately, the prognosis is excellent if detected at an early stage. Hence, the detection and localization of prostate cancer is crucial for diagnosis, as well as treatment via targeted focal therapy. New imaging techniques can potentially be invaluable tools for improving prostate cancer detection and localization. METHODS: In this study, we introduce a new form of diffusion magnetic resonance imaging called correlated diffusion imaging, where the tissue being imaged is characterized by the joint correlation of diffusion signal attenuation across multiple gradient pulse strengths and timings. By taking into account signal attenuation at different water diffusion motion sensitivities, correlated diffusion imaging can provide improved delineation between cancerous tissue and healthy tissue when compared to existing diffusion imaging modalities. RESULTS: Quantitative evaluation using receiver operating characteristic (ROC) curve analysis, tissue class separability analysis, and visual assessment by an expert radiologist were performed to study correlated diffusion imaging for the task of prostate cancer diagnosis. These results are compared with that obtained using T2-weighted imaging and standard diffusion imaging (via the apparent diffusion coefficient (ADC)). Experimental results suggest that correlated diffusion imaging provide improved delineation between healthy and cancerous tissue and may have potential as a diagnostic tool for cancer detection and localization in the prostate gland. CONCLUSIONS: A new form of diffusion magnetic resonance imaging called correlated diffusion imaging (CDI) was developed for the purpose of aiding radiologists in cancer detection and localization in the prostate gland. Preliminary results show CDI shows considerable promise as a diagnostic aid for radiologists in the detection and localization of prostate cancer.

Quantitative vibratory sensation measurement is related to sensory cortical thickness in MS.

Objective: Vibratory sensation is a quantifiable measure of physical dysfunction and is often related to spinal cord pathology; however, its association with relevant brain areas has not been fully explored. Our objective was to establish a cortical structural substrate for vibration sensation. Methods: Eighty-four individuals with multiple sclerosis (MS) (n = 54 relapsing, n = 30 progressive) and 28 controls participated in vibratory sensation threshold quantification at the great toe and a 3T MRI evaluating volume of the thalamus and cortical thickness primary and secondary sensory cortices. Results: After controlling for age, sex, and disability level, vibratory sensation thresholds were significantly related to cortical thickness of the anterior cingulate (P = 0.041), parietal operculum (P = 0.022), and inferior frontal gyrus pars operculum (P = 0.044), pars orbitalis (P = 0.007), and pars triangularis (P = 0.029). Within the progressive disease subtype, there were significant relationships between vibratory sensation and thalamic volume (P = 0.039) as well as reduced inferior frontal gyrus pars operculum (P = 0.014) and pars orbitalis (P = 0.005) cortical thickness. Conclusions: The data show significant independent relationships between quantitative vibratory sensation and measures of primary and secondary sensory cortices. Quantitative clinical measurement of vibratory sensation reflects pathological changes in spatially distinct brain areas and may supplement information captured by brain atrophy measures. Without overt relapses, monitoring decline in progressive forms of MS has proved challenging; quantitative clinical assessment may provide a tool to examine pathological decline in this cohort. These data suggest that quantitative clinical assessment may be a reliable way to examine pathological decline and have broader relevance to progressive forms of MS.

Deformable model reconstruction of the subarachnoid space.

The subarachnoid space is a layer in the meninges that surrounds the brain and is filled with trabeculae and cerebrospinal fluid. Quantifying the volume and thickness of the subarachnoid space is of interest in order to study the pathogenesis of neurodegenerative diseases and compare with healthy subjects. We present an automatic method to reconstruct the subarachnoid space with subvoxel accuracy using a nested deformable model. The method initializes the deformable model using the convex hull of the union of the outer surfaces of the cerebrum, cerebellum and brainstem. A region force is derived from the subject's Tl-weighted and T2-weighted MRI to drive the deformable model to the outer surface of the subarachnoid space. The proposed method is compared to a semi-automatic delineation from the subject's T2-weighted MRI and an existing multi-atlas-based method. A small pilot study comparing the volume and thickness measurements in a set of age-matched subjects with normal pressure hydrocephalus and healthy controls is presented to show the efficacy of the proposed method.

Automatic falx cerebri and tentorium cerebelli segmentation from Magnetic Resonance Images.

The falx cerebri and tentorium cerebelli are dural structures found in the brain. Due to the roles both structures play in constraining brain motion, the falx and tentorium must be identified and included in finite element models of the head to accurately predict brain dynamics during injury events. To date there has been very little research work on automatically segmenting these two structures, which is understandable given that their 1) thin structure challenges the resolution limits of in vivo 3D imaging, and 2) contrast with respect to surrounding tissue is low in standard magnetic resonance imaging. An automatic segmentation algorithm to find the falx and tentorium which uses the results of a multi-atlas segmentation and cortical reconstruction algorithm is proposed. Gray matter labels are used to find the location of the falx and tentorium. The proposed algorithm is applied to five datasets with manual delineations. 3D visualizations of the final results are provided, and Hausdorff distance (HD) and mean surface distance (MSD) is calculated to quantify the accuracy of the proposed method. For the falx, the mean HD is 43.84 voxels and the mean MSD is 2.78 voxels, with the largest errors occurring at the frontal inferior falx boundary. For the tentorium, the mean HD is 14.50 voxels and mean MSD is 1.38 voxels.

Falx Cerebri Segmentation via Multi-atlas Boundary Fusion.

The falx cerebri is a meningeal projection of dura in the brain, separating the cerebral hemispheres. It has stiffer mechanical properties than surrounding tissue and must be accurately segmented for building computational models of traumatic brain injury. In this work, we propose a method to segment the falx using T1-weighted magnetic resonance images (MRI) and susceptibility-weighted MRI (SWI). Multi-atlas whole brain segmentation is performed using the T1-weighted MRI and the gray matter cerebrum labels are extended into the longitudinal fissure using fast marching to find an initial estimate of the falx. To correct the falx boundaries, we register and then deform a set of SWI with manually delineated falx boundaries into the subject space. The continuous-STAPLE algorithm fuses sets of corresponding points to produce an estimate of the corrected falx boundary. Correspondence between points on the deformed falx boundaries is obtained using coherent point drift. We compare our method to manual ground truth, a multi-atlas approach without correction, and single-atlas approaches.

Segmentation of Thalamus from MR images via Task-Driven Dictionary Learning.

Automatic thalamus segmentation is useful to track changes in thalamic volume over time. In this work, we introduce a task-driven dictionary learning framework to find the optimal dictionary given a set of eleven features obtained from T1-weighted MRI and diffusion tensor imaging. In this dictionary learning framework, a linear classifier is designed concurrently to classify voxels as belonging to the thalamus or non-thalamus class. Morphological post-processing is applied to produce the final thalamus segmentation. Due to the uneven size of the training data samples for the non-thalamus and thalamus classes, a non-uniform sampling scheme is proposed to train the classifier to better discriminate between the two classes around the boundary of the thalamus. Experiments are conducted on data collected from 22 subjects with manually delineated ground truth. The experimental results are promising in terms of improvements in the Dice coefficient of the thalamus segmentation over state-of-the-art atlas-based thalamus segmentation algorithms.

Thalamus parcellation using multi-modal feature classification and thalamic nuclei priors.

Segmentation of the thalamus and thalamic nuclei is useful to quantify volumetric changes from neurodegenerative diseases. Most thalamus segmentation algorithms only use T1-weighted magnetic resonance images and current thalamic parcellation methods require manual interaction. Smaller nuclei, such as the lateral and medial geniculates, are challenging to locate due to their small size. We propose an automated segmentation algorithm using a set of features derived from diffusion tensor image (DTI) and thalamic nuclei location priors. After extracting features, a hierarchical random forest classifier is trained to locate the thalamus. A second random forest classifies thalamus voxels as belonging to one of six thalamic nuclei classes. The proposed algorithm was tested using a leave-one-out cross validation scheme and compared with state-of-the-art algorithms. The proposed algorithm has a higher Dice score compared to other methods for the whole thalamus and several nuclei.

PROBABILISTIC FIBER TRACKING USING A MODIFIED LASSO BOOTSTRAP METHOD.

Diffusion MRI (dMRI) provides a noninvasive tool for investigating white matter tracts. Probabilistic fiber tracking has been proposed to represent the fiber structures as 3D streamlines while taking the uncertainty introduced by noise into account. In this paper, we propose a probabilistic fiber tracking method based on bootstrapping a multi-tensor model with a fixed tensor basis. The fiber orientation (FO) estimation is formulated as a Lasso problem. Then by resampling the residuals calculated using a modified Lasso estimator to create synthetic diffusion signals, a distribution of FOs is estimated. Probabilistic fiber tracking can then be performed by sampling from the FO distribution. Experiments were performed on a digital crossing phantom and brain dMRI for validation.

High-level intuitive features (HLIFs) for intuitive skin lesion description.

A set of high-level intuitive features (HLIFs) is proposed to quantitatively describe melanoma in standard camera images. Melanoma is the deadliest form of skin cancer. With rising incidence rates and subjectivity in current clinical detection methods, there is a need for melanoma decision support systems. Feature extraction is a critical step in melanoma decision support systems. Existing feature sets for analyzing standard camera images are comprised of low-level features, which exist in high-dimensional feature spaces and limit the system's ability to convey intuitive diagnostic rationale. The proposed HLIFs were designed to model the ABCD criteria commonly used by dermatologists such that each HLIF represents a human-observable characteristic. As such, intuitive diagnostic rationale can be conveyed to the user. Experimental results show that concatenating the proposed HLIFs with a full low-level feature set increased classification accuracy, and that HLIFs were able to separate the data better than low-level features with statistical significance. An example of a graphical interface for providing intuitive rationale is given.

Segmentation of skin lesions from digital images using joint statistical texture distinctiveness.

Melanoma is the deadliest form of skin cancer. Incidence rates of melanoma have been increasing, especially among non-Hispanic white males and females, but survival rates are high if detected early. Due to the costs for dermatologists to screen every patient, there is a need for an automated system to assess a patient's risk of melanoma using images of their skin lesions captured using a standard digital camera. One challenge in implementing such a system is locating the skin lesion in the digital image. A novel texture-based skin lesion segmentation algorithm is proposed. A set of representative texture distributions are learned from an illumination-corrected photograph and a texture distinctiveness metric is calculated for each distribution. Next, regions in the image are classified as normal skin or lesion based on the occurrence of representative texture distributions. The proposed segmentation framework is tested by comparing lesion segmentation results and melanoma classification results to results using other state-of-art algorithms. The proposed framework has higher segmentation accuracy compared to all other tested algorithms.

Monte Carlo bias field correction in endorectal diffusion imaging.

Prostate cancer is one of the leading causes of cancer death in the male population. The detection of prostate cancer using imaging has been challenging until recently. Multiparametric magnetic resonance imaging (MRI) has been shown to allow accurate localization of the cancers and can help direct biopsies to cancer foci, which is required to plan the treatment. The interpretation of MRI, however, requires a high level of expertise and review of large multiparametric datasets. An endorectal receiver coil is often used to improve signal-to-noise ratio and aid in detection of smaller cancer foci. Moreover, computed high b-value diffusion-weighted imaging show improved delineation of tumors but is subject to strong bias fields near the coil. Here, a nonparametric approach to bias field correction for endorectal diffusion imaging via Monte Carlo sampling is introduced. It will be shown that the delineation between the prostate gland and the background and intensity inhomogeneity may be improved using the proposed approach. High b-value generated results also show improved visualization of tumor regions. The results suggest that Monte Carlo bias correction may have potential as a preprocessing tool for endorectal diffusion images for the prostate cancer detection and localization or segmentation.

Automatic method for thalamus parcellation using multi-modal feature classification.

Segmentation and parcellation of the thalamus is an important step in providing volumetric assessment of the impact of disease n brain structures. Conventionally, segmentation is carried out on T1-weighted magnetic resonance (MR) images and nuclear parcellation using diffusion weighted MR images. We present the first fully automatic method that incorporates both tissue contrasts and several derived fea-fractional anisotrophy, fiber orientation from the 5D Knutsson representation of the principal eigenvectors, and connectivity between the thalamus and the cortical lobes, as features. Combining these multiple information sources allows us to identify discriminating dimensions and thus parcellate the thalamic nuclei. A hierarchical random forest framework with a multidimensional feature per voxel, first distinguishes thalamus from background, and then separates each group of thalamic nuclei. Using a leave one out cross-validation on 12 subjects we have a mean Dice score of 0.805 and 0.799 for the left and right thalami, respectively. We also report overlap for the thalamic nuclear groups.

MSIM: multistage illumination modeling of dermatological photographs for illumination-corrected skin lesion analysis.

Melanoma is the most deadly form of skin cancer and it is costly for dermatologists to screen every patient for melanoma. There is a need for a system to assess the risk of melanoma based on dermatological photographs of a skin lesion. However, the presence of illumination variation in the photographs can have a negative impact on lesion segmentation and classification performance. A novel multistage illumination modeling algorithm is proposed to correct the underlying illumination variation in skin lesion photographs. The first stage is to compute an initial estimate of the illumination map of the photograph using a Monte Carlo nonparametric modeling strategy. The second stage is to obtain a final estimate of the illumination map via a parametric modeling strategy, where the initial nonparametric estimate is used as a prior. Finally, the corrected photograph is obtained using the final illumination map estimate. The proposed algorithm shows better visual, segmentation, and classification results when compared to three other illumination correction algorithms, one of which is designed specifically for lesion analysis.

Stochastic speckle noise compensation in optical coherence tomography using non-stationary spline-based speckle noise modelling.

Optical coherence tomography (OCT) allows for non-invasive 3D visualization of biological tissue at cellular level resolution. Often hindered by speckle noise, the visualization of important biological tissue details in OCT that can aid disease diagnosis can be improved by speckle noise compensation. A challenge with handling speckle noise is its inherent non-stationary nature, where the underlying noise characteristics vary with the spatial location. In this study, an innovative speckle noise compensation method is presented for handling the non-stationary traits of speckle noise in OCT imagery. The proposed approach centers on a non-stationary spline-based speckle noise modeling strategy to characterize the speckle noise. The novel method was applied to ultra high-resolution OCT (UHROCT) images of the human retina and corneo-scleral limbus acquired in-vivo that vary in tissue structure and optical properties. Test results showed improved performance of the proposed novel algorithm compared to a number of previously published speckle noise compensation approaches in terms of higher signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and better overall visual assessment.

Illumination correction in dermatological photographs using multi-stage illumination modeling for skin lesion analysis.

A novel algorithm for correcting illumination variation in dermatological photographs via a multi-stage modeling of the underlying illumination is proposed for the purpose of skin lesion analysis. First, an initial illumination estimate is obtained via a non-parametric modeling strategy based on Monte Carlo sampling. Next, a subset of pixels from the non-parametric estimate is used to determine a parametric estimate of the illumination based on a quadratic surface model. Using the parametric illumination estimate, the reflectance map is obtained and used to correct the photograph. The photographs corrected using the proposed algorithm are compared to uncorrected photographs and to a state-of-the-art correction algorithm. Qualitatively, a visual comparison is performed, while quantitatively, the coefficient of variation of skin pixel intensities is calculated and the precision-recall curve for segmentation of skin lesions is graphed. Results show that the proposed algorithm has a lower coefficient of variation and an improved precision-recall curve.

Non-parametric Bayesian estimation of apparent diffusion coefficient from diffusion-weighted magnetic resonance imaging data.

A promising approach to prostate cancer diagnosis is multi-parametric MRI. One of the key modalities used in multi-parametric MRI is diffusion weighted MRI. Using multiple diffusion weighted MR acquisitions taken with different magnetic gradient strengths, the apparent diffusion coefficient (ADC) is calculated and can be used to identify tumors in the prostate. Current algorithms used to calculate ADC assume a parametric measurement model, but this assumption is not true due to the presence of additional phenomena during the acquisition process. A novel Non-parametric Estimated ADC (NEstA) algorithm is proposed which uses a Monte Carlo strategy to learn the inherent measurement distribution model based on the underlying statistical behavior of the DWI measurements to estimate the ADC values. The proposed algorithm is compared to the results of the commonly used least-squares (LS) estimation algorithm for computing ADC values. Nine test patient cases with visible tumors in the prostate gland were processed using both algorithms and compared visually. It was found that NEstA produced ADC data with reduced artifacts while preserving structure. Quantitatively, Fisher's criterion measuring the separability of the healthy prostate and tumor tissues was computed for the nine patient cases, comparing the NEstA and LS methods. It was found that Fisher's criterion increased with the NEstA method, meaning the separation of classes was more pronounced.

Quantitative investigative analysis of tumour separability in the prostate gland using ultra-high b-value computed diffusion imaging.

High b-value diffusion-weighted imaging is a promising approach for diagnosing and localizing cancer in the prostate gland. However, ultra-high b-value imaging is difficult to achieve at a high signal-to-noise ratio due to hardware limitations. An alternative approach being recently discussed is computed diffusion-weighted imaging, which allows for estimation of ultra-high b-value images from a set of diffusion-weighted acquisitions with different magnetic gradient strengths. This paper presents a quantitative investigative analysis of the improvement in tumour separability in the prostate gland from using ultra-high b-value computed diffusion-weighted imaging. The analysis computes ultra-high b-value images for six patient cases and investigates the separability of the tumour from the normal prostate gland. Based on quantitative metrics such as expected probability of classification error and the Receiver Operating Characteristic (ROC), it was found that the use of ultra-high computed diffusion-weighted imaging may significantly improve tumour separability, with a b-value around 3000 providing optimal separability.