Simultaneous Depth Estimation and Surgical Tool Segmentation in Laparoscopic Images.

Surgical instrument segmentation and depth estimation are crucial steps to improve autonomy in robotic surgery. Most recent works treat these problems separately, making the deployment challenging. In this paper, we propose a unified framework for depth estimation and surgical tool segmentation in laparoscopic images. The network has an encoder-decoder architecture and comprises two branches for simultaneously performing depth estimation and segmentation. To train the network end to end, we propose a new multi-task loss function that effectively learns to estimate depth in an unsupervised manner, while requiring only semi-ground truth for surgical tool segmentation. We conducted extensive experiments on different datasets to validate these findings. The results showed that the end-to-end network successfully improved the state-of-the-art for both tasks while reducing the complexity during their deployment.

Prospective testing of clinical Cerenkov luminescence imaging against standard-of-care nuclear imaging for tumour location.

In oncology, the feasibility of Cerenkov luminescence imaging (CLI) has been assessed by imaging superficial lymph nodes in a few patients undergoing diagnostic 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). However, the weak luminescence signal requires the removal of ambient light. Here we report the development of a clinical CLI fiberscope with a lightproof enclosure, and the clinical testing of the setup using five different radiotracers. In an observational prospective trial (ClinicalTrials.gov identifier NCT03484884 ) involving 96 patients with existing or suspected tumours, scheduled for routine clinical FDG PET or 131I therapy, the level of agreement of CLI with standard-of-care imaging (PET or planar single-photon emission CT) for tumour location was 'acceptable' or higher (≥3 in the 1-5 Likert scale) for 90% of the patients. CLI correlated with the concentration of radioactive activity, and captured therapeutically relevant information from patients undergoing targeted radiotherapy or receiving the alpha emitter 223Ra, which cannot be feasibly imaged clinically. CLI could supplement radiological scans, especially when scanner capacity is limited.

In situ lymphoma imaging in a spontaneous mouse model using the Cerenkov Luminescence of F-18 and Ga-67 isotopes.

Cerenkov luminescence imaging (CLI) is a promising approach to image-guided surgery and pathological sampling. It could offer additional advantages when combined to whole-body isotope tomographies. We aimed to obtain evidence of its applicability in lymphoma patho-diagnostics, thus we decided to investigate the radiodiagnostic potential of combined PET or SPECT/CLI in an experimental, novel spontaneous high-grade B-cell lymphoma mouse model (Bc.DLFL1). We monitored the lymphoma dissemination at early stage, and at clinically relevant stages such as advanced stage and terminal stage with in vivo 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) and 67Ga-citrate single photon emission computed tomography (SPECT)/MRI. In vivo imaging was combined with ex vivo high resolution CLI. The use of CLI with 18F-Fluorine (F-18) and 67Ga-Gallium isotopes in the selection of infiltrated lymph nodes for tumor staging and pathology was thus tested. At advanced stage, FDG PET/MRI plus ex vivo CLI allowed accurate detection of FDG accumulation in lymphoma-infiltrated tissues. At terminal stage we detected tumorous lymph nodes with SPECT/MRI and we could report in vivo detection of the Cerenkov light emission of 67Ga. CLI with 67Ga-citrate revealed lymphoma accumulation in distant lymph node locations, unnoticeable with only MRI. Flow cytometry and immunohistochemistry confirmed these imaging results. Our study promotes the combined use of PET and CLI in preclinical studies and clinical practice. Heterogeneous FDG distribution in lymph nodes, detected at sampling surgery, has implications for tissue pathology processing and it could direct therapy. The results with 67Ga also point to the opportunities to further apply suitable SPECT radiopharmaceuticals for CLI.

Intraperitoneal Glucose Transport to Micrometastasis: A Multimodal In Vivo Imaging Investigation in a Mouse Lymphoma Model.

Bc-DLFL.1 is a novel spontaneous, high-grade transplantable mouse B-cell lymphoma model for selective serosal propagation. These cells attach to the omentum and mesentery and show dissemination in mesenteric lymph nodes. We aimed to investigate its early stage spread at one day post-intraperitoneal inoculation of lymphoma cells (n = 18 mice), and its advanced stage at seven days post-inoculation with in vivo [18F]FDG-PET and [18F]PET/MRI, and ex vivo by autoradiography and Cherenkov luminescence imaging (CLI). Of the early stage group, nine animals received intraperitoneal injections, and nine received intravenous [18F]FDG injections. The advanced stage group (n = 3) received intravenous FDG injections. In the early stage, using autoradiography we observed a marked accumulation in the mesentery after intraperitoneal FDG injection. Using other imaging methods and autoradiography, following the intravenous injection of FDG no accumulations were detected. At the advanced stage, tracer accumulation was clearly detected in mesenteric lymph nodes and in the peritoneum after intravenous administration using PET. We confirmed the results with immunohistochemistry. Our results in this model highlight the importance of local FDG administration during diagnostic imaging to precisely assess early peritoneal manifestations of other malignancies (colon, stomach, ovary). These findings also support the importance of applying topical therapies, in addition to systemic treatments in peritoneal cancer spread.

Tracking and visualization of the sensing area for a tethered laparoscopic gamma probe.

PURPOSE: In surgical oncology, complete cancer resection and lymph node identification are challenging due to the lack of reliable intraoperative visualization. Recently, endoscopic radio-guided cancer resection has been introduced where a novel tethered laparoscopic gamma detector can be used to determine the location of tracer activity, which can complement preoperative nuclear imaging data and endoscopic imaging. However, these probes do not clearly indicate where on the tissue surface the activity originates, making localization of pathological sites difficult and increasing the mental workload of the surgeons. Therefore, a robust real-time gamma probe tracking system integrated with augmented reality is proposed. METHODS: A dual-pattern marker has been attached to the gamma probe, which combines chessboard vertices and circular dots for higher detection accuracy. Both patterns are detected simultaneously based on blob detection and the pixel intensity-based vertices detector and used to estimate the pose of the probe. Temporal information is incorporated into the framework to reduce tracking failure. Furthermore, we utilized the 3D point cloud generated from structure from motion to find the intersection between the probe axis and the tissue surface. When presented as an augmented image, this can provide visual feedback to the surgeons. RESULTS: The method has been validated with ground truth probe pose data generated using the OptiTrack system. When detecting the orientation of the pose using circular dots and chessboard dots alone, the mean error obtained is [Formula: see text] and [Formula: see text], respectively. As for the translation, the mean error for each pattern is 1.78 mm and 1.81 mm. The detection limits for pitch, roll and yaw are [Formula: see text] and [Formula: see text]-[Formula: see text]-[Formula: see text] . CONCLUSION: The performance evaluation results show that this dual-pattern marker can provide high detection rates, as well as more accurate pose estimation and a larger workspace than the previously proposed hybrid markers. The augmented reality will be used to provide visual feedback to the surgeons on the location of the affected lymph nodes or tumor.

Intraoperative Assessment of Tumor Resection Margins in Breast-Conserving Surgery Using 18F-FDG Cerenkov Luminescence Imaging: A First-in-Human Feasibility Study.

In early-stage breast cancer, the primary treatment option for most women is breast-conserving surgery (BCS). There is a clear need for more accurate techniques to assess resection margins intraoperatively, because on average 20% of patients require further surgery to achieve clear margins. Cerenkov luminescence imaging (CLI) combines optical and molecular imaging by detecting light emitted by 18F-FDG. Its high-resolution and small size imaging equipment make CLI a promising technology for intraoperative margin assessment. A first-in-human study was conducted to evaluate the feasibility of 18F-FDG CLI for intraoperative assessment of tumor margins in BCS. Methods: Twenty-two patients with invasive breast cancer received 18F-FDG (5 MBq/kg) 45-60 min before surgery. Sentinel lymph node biopsy was performed using an increased 99mTc-nanocolloid activity of 150 MBq to facilitate nodal detection against the γ-probe background signal (cross-talk) from 18F-FDG. The cross-talk and 99mTc dose required was evaluated in 2 lead-in studies. Immediately after excision, specimens were imaged intraoperatively in an investigational CLI system. The first 10 patients were used to optimize the imaging protocol; the remaining 12 patients were included in the analysis dataset. Cerenkov luminescence images from incised BCS specimens were analyzed postoperatively by 2 surgeons blinded to the histopathology results, and mean radiance and margin distance were measured. The agreement between margin distance on CLI and histopathology was assessed. Radiation doses to staff were measured. Results: Ten of the 12 patients had an elevated tumor radiance on CLI. Mean radiance and tumor-to-background ratio were 560 ± 160 photons/s/cm2/sr and 2.41 ± 0.54, respectively. All 15 assessable margins were clear on CLI and histopathology. The agreement in margin distance and interrater agreement was good (κ = 0.81 and 0.912, respectively). Sentinel lymph nodes were successfully detected in all patients. The radiation dose to staff was low; surgeons received a mean dose of 34 ± 15 µSv per procedure. Conclusion: Intraoperative 18F-FDG CLI is a promising, low-risk technique for intraoperative assessment of tumor margins in BCS. A randomized controlled trial will evaluate the impact of this technique on reexcision rates.

RAMP: a bioinformatics framework for researching imaging agents through molecular pathways.

Signaling pathways are the fundamental grammar of cellular communication, yet few frameworks are available to analyze molecular imaging probes in the context of signaling pathways. Such a framework would aid in the design and selection of imaging probes for measuring specific signaling pathways and, vice versa, help illuminate which pathways are being assayed by a given probe. RAMP (Researching imaging Agents through Molecular Pathways) is a bioinformatics framework for connecting signaling pathways and imaging probes using a controlled vocabulary of the imaging targets. RAMP contains signaling pathway data from MetaCore, the Kyoto Encyclopedia of Genes and Genomes, and the Gene Ontology project; imaging probe data from the Molecular Imaging and Contrast Agent Database (MICAD); and tissue protein expression data from The Human Protein Atlas. The RAMP search tool is available at . Examples are presented to demonstrate the utility of RAMP for pathway-based searches of molecular imaging probes.

Focal reversible deactivation of cerebral metabolism affects water diffusion.

The underlying biophysical mechanisms which affect cerebral diffusion contrast remain poorly understood. We hypothesized that cerebral metabolism may affect cerebral diffusion contrast. The purpose of this study was to develop the methodology to reversibly deactivate cerebral metabolism and measure the effect on the diffusion MRI signal. We developed an MRI-compatible cortical cooling system to reversibly deactivate cortical metabolism in rhesus monkey area V1 and used MR thermometry to calculate three-dimensional temperature maps of the brain to define the extent of deactivated brain in vivo. Significant changes in the apparent diffusion coefficient (ADC) were only observed during those experiments in which the cortex was cooled below the metabolic cutoff temperature of 20 degrees C. ADC decreases (12-20%) were observed during cortical cooling in regions where the temperature did not change. The normalized in vivo ADC as function of temperature was measured and found to be equivalent to the normalized ADC of free water at temperatures above 20 degrees C, but was significantly decreased below 20 degrees C (20-25% decrease). No changes in fractional anisotropy were observed. In future experiments, we will apply this methodology to quantify the effect of reversible deactivation on neural activity as measured by the hemodynamic response and compare water diffusion changes with hemodynamic changes.

Response monitoring, repetitive behaviour and anterior cingulate abnormalities in autism spectrum disorders (ASD).

Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing factors to autistic disorders. We investigated whether ACC structure and function during response monitoring were associated with repetitive behaviour in ASD. We compared ACC activation to correct and erroneous antisaccades using rapid presentation event-related functional MRI in 14 control and ten ASD participants. Because response monitoring is the product of coordinated activity in ACC networks, we also examined the microstructural integrity of the white matter (WM) underlying this brain region using diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) in 12 control and 12 adult ASD participants. ACC activation and FA were examined in relation to Autism Diagnostic Interview-Revised ratings of restricted and repetitive behaviour. Relative to controls, ASD participants: (i) made more antisaccade errors and responded more quickly on correct trials; (ii) showed reduced discrimination between error and correct responses in rostral ACC (rACC), which was primarily due to (iii) abnormally increased activation on correct trials and (iv) showed reduced FA in WM underlying ACC. Finally, in ASD (v) increased activation on correct trials and reduced FA in rACC WM were related to higher ratings of repetitive behaviour. These findings demonstrate functional and structural abnormalities of the ACC in ASD that may contribute to repetitive behaviour. rACC activity following errors is thought to reflect affective appraisal of the error. Thus, the hyperactive rACC response to correct trials can be interpreted as a misleading affective signal that something is awry, which may trigger repetitive attempts at correction. Another possible consequence of reduced affective discrimination between error and correct responses is that it might interfere with the reinforcement of responses that optimize outcomes. Furthermore, dysconnection of the ACC, as suggested by reduced FA, to regions involved in behavioural control might impair on-line modulations of response speed to optimize performance (i.e. speed-accuracy trade-off) and increase error likelihood. These findings suggest that in ASD, structural and functional abnormalities of the ACC compromise response monitoring and thereby contribute to behaviour that is rigid and repetitive rather than flexible and responsive to contingencies. Illuminating the mechanisms and clinical significance of abnormal response monitoring in ASD represents a fruitful avenue for further research.

A non-invasive method to relate the timing of neural activity to white matter microstructural integrity.

The neurophysiological basis of variability in the latency of evoked neural responses has been of interest for decades. We describe a method to identify white matter pathways that may contribute to inter-individual variability in the timing of neural activity. We investigated the relation of the latency of peak visual responses in occipital cortex as measured by magnetoencephalography (MEG) to fractional anisotropy (FA) in the entire brain as measured with diffusion tensor imaging (DTI) in eight healthy young adults. This method makes no assumptions about the anatomy of white matter connections. Visual responses were evoked during a saccadic paradigm and were time-locked to arrival at a saccadic goal. The latency of the peak visual response was inversely related to FA in bilateral parietal and right lateral frontal white matter adjacent to cortical regions that modulate early visual responses. These relations suggest that biophysical properties of white matter affect the timing of early visual responses. This preliminary report demonstrates a non-invasive, unbiased method to relate the timing information from evoked-response experiments to the biophysical properties of white matter measured with DTI.

Using the wild bootstrap to quantify uncertainty in diffusion tensor imaging.

Estimation of noise-induced variability in diffusion tensor imaging (DTI) is needed to objectively follow disease progression in therapeutic monitoring and to provide consistent readouts of pathophysiology. The noise variability of nonlinear quantities of the diffusion tensor (e.g., fractional anisotropy, fiber orientation, etc.) have been quantified using the bootstrap, in which the data are resampled from the experimental averages, yet this approach is only applicable to DTI scans that contain multiple averages from the same sampling direction. It has been shown that DTI acquisitions with a modest to large number of directions, in which each direction is only sampled once, outperform the multiple averages approach. These acquisitions resist the traditional (regular) bootstrap analysis though. In contrast to the regular bootstrap, the wild bootstrap method can be applied to such protocols in which there is only one observation per direction. Here, we compare and contrast the wild bootstrap with the regular bootstrap using Monte Carlo numerical simulations for a number of diffusion scenarios. The regular and wild bootstrap methods are applied to human DTI data and empirical distributions are obtained for fractional anisotropy and the diffusion tensor eigensystem. Spatial maps of the estimated variability in the diffusion tensor principal eigenvector are provided. The wild bootstrap method can provide empirical distributions for tensor-derived quantities, such as fractional anisotropy and principal eigenvector direction, even when the exact distributions are not easily derived.

Reduced microstructural integrity of the white matter underlying anterior cingulate cortex is associated with increased saccadic latency in schizophrenia.

The anterior cingulate cortex (ACC) is a key component of a network that directs both spatial attention and saccadic eye movements, which are tightly linked. Diffusion tensor imaging (DTI) has demonstrated reduced microstructural integrity of the anterior cingulum bundle as indexed by fractional anisotropy (FA) in schizophrenia, but the functional significance of these abnormalities is unclear. Using DTI, we examined the white matter underlying anterior cingulate cortex in schizophrenia to determine whether reduced FA is associated with prolonged latencies of volitional saccades. Seventeen chronic, medicated schizophrenia outpatients and nineteen healthy controls had high-resolution DTI scans. FA maps were registered to structural scans and mapped across participants using a surface-based coordinate system. Cingulate white matter was divided into rostral and dorsal anterior regions and a posterior region. Patients showed reduced FA in cingulate white matter of the right hemisphere. Reduced FA in the white matter underlying anterior cingulate cortex, frontal eye field, and posterior parietal cortex of the right hemisphere was associated with longer saccadic latencies in schizophrenia, though given the relatively small sample size, these relations warrant replication. These findings demonstrate that in schizophrenia, increased latency of volitional saccades is associated with reduced microstructural integrity of the white matter underlying key cortical components of a right-hemisphere dominant network for visuospatial attention and ocular motor control. Moreover, they suggest that anterior cingulate white matter abnormalities contribute to slower performance of volitional saccades and to inter-individual variability of saccadic latency in chronic, medicated schizophrenia.

Statistical group comparison of diffusion tensors via multivariate hypothesis testing.

Diffusion tensor imaging (DTI) provides a powerful tool for identifying white matter (WM) alterations in clinical populations. The prevalent method for group-level analysis of DTI is statistical comparison of the diffusion tensor fractional anisotropy (FA) metric. The FA metric, however, does not capture the full orientational information contained in the diffusion tensor. For example, the FA test is incapable of detecting group-level differences in diffusion orientation when the level of anisotropy is unaffected. Here, we apply multivariate hypothesis testing procedures to the elements of the diffusion tensor as an alternative to univariate testing using FA. Both parametric and nonparametric tests are proposed with each choice carrying specific assumptions about the diffusion tensor model. Of particular interest is the Cramér test, which works on Euclidean interpoint distances and can be readily adapted to a specific non-Euclidean framework by applying matrix logarithms to the diffusion tensors. Using Monte Carlo simulations, we show that multivariate tests can detect diffusion tensor principal eigenvector differences of 15 degrees with up to 80-90% power under typical design conditions. We also show that some multivariate tests are more sensitive to FA differences, when compared to a univariate test on FA, even if there is no principal eigenvector difference. The Cramér test, using the Euclidean interpoint distances, performed best under both simulation scenarios. When applying the Cramér test of the diffusion tensor in a clinical population with a history of migraine, a 169% increase was observed in the volume of a significant cluster compared to the univariate FA test.

Interictal alterations of the trigeminal somatosensory pathway and periaqueductal gray matter in migraine.

Migraine has been traditionally considered a nonprogressive, paroxysmal disorder with no brain abnormalities between attacks. We used diffusion tensor imaging to examine interictal diffusion properties of the brains of migraineurs with aura, migraineurs without aura and matched healthy controls. Areas of lower fractional anisotropy were present in migraineurs along the thalamocortical tract. In addition, migraineurs with aura had lower fractional anisotropy in the ventral trigeminothalamic tract, and migraineurs without aura had lower fractional anisotropy in the ventrolateral periaqueductal grey matter. Our results indicate the presence of permanent interictal changes in migraineurs, pointing to an effect of migraine on the trigeminal somatosensory and modulatory pain systems.

Boosting the sampling efficiency of q-Ball imaging using multiple wavevector fusion.

q-Ball imaging (QBI) is a high-angular-resolution diffusion imaging (HARDI) method that is capable of resolving complex, subvoxel white matter (WM) architecture. QBI requires time-intensive sampling of the diffusion signal and large diffusion wavevectors. Here we describe a reconstruction scheme for QBI, termed multiple wavevector fusion (MWF), that substantially boosts the sampling efficiency and signal-to-noise ratio (SNR) of QBI. The MWF reconstruction operates by nonlinearly fusing the diffusion signal from separate low and high wavevector acquisitions. The combination of wavevectors provides the benefits of the high SNR of the low wavevector signal and the high angular contrast-to-noise ratio (CNR) and peak separation of the high wavevector signal. The MWF procedure provides a framework for combining diffusion tensor imaging (DTI) and QBI. Numerical simulations show that MWF of DTI and QBI provides a more accurate estimate of the diffusion orientation distribution function (ODF) than QBI alone. The accuracy improvement can be translated into an efficiency gain of 274-377%. An intravoxel peak connectivity metric (IPCM) is presented that calculates the peak connectivity between an ODF and its neighboring voxels. In human WM, MWF reveals more detailed WM architecture than QBI as measured by the IPCM for all sampling schemes presented.

Frontal connections and cognitive changes in normal aging rhesus monkeys: a DTI study.

Recent anatomical studies have found that cortical neurons are mainly preserved during the aging process while myelin damage and even axonal loss is prominent throughout the forebrain. We used diffusion tensor imaging (DT-MRI) to evaluate the hypothesis that during the process of normal aging, white matter changes preferentially affect the integrity of long corticocortical association fiber tracts, specifically the superior longitudinal fasciculus II and the cingulum bundle. This would disrupt communication between the frontal lobes and other forebrain regions leading to cognitive impairments. We analyzed DT-MRI datasets from seven young and seven elderly behaviorally characterized rhesus monkeys, creating fractional anisotropy (FA) maps of the brain. Significant age-related reductions in mean FA values were found for the superior longitudinal fasciculus II and the cingulum bundle, as well as the anterior corpus callosum. Comparison of these FA reductions with behavioral measures demonstrated a statistically significant linear relationship between regional FA and performance on a test of executive function. These findings support the hypothesis that alterations to the integrity of these long association pathways connecting the frontal lobe with other forebrain regions contribute to cognitive impairments in normal aging. To our knowledge this is the first investigation reporting such alterations in the aging monkey.

Anatomical alterations of the visual motion processing network in migraine with and without aura.

BACKGROUND: Patients suffering from migraine with aura (MWA) and migraine without aura (MWoA) show abnormalities in visual motion perception during and between attacks. Whether this represents the consequences of structural changes in motion-processing networks in migraineurs is unknown. Moreover, the diagnosis of migraine relies on patient's history, and finding differences in the brain of migraineurs might help to contribute to basic research aimed at better understanding the pathophysiology of migraine. METHODS AND FINDINGS: To investigate a common potential anatomical basis for these disturbances, we used high-resolution cortical thickness measurement and diffusion tensor imaging (DTI) to examine the motion-processing network in 24 migraine patients (12 with MWA and 12 MWoA) and 15 age-matched healthy controls (HCs). We found increased cortical thickness of motion-processing visual areas MT+ and V3A in migraineurs compared to HCs. Cortical thickness increases were accompanied by abnormalities of the subjacent white matter. In addition, DTI revealed that migraineurs have alterations in superior colliculus and the lateral geniculate nucleus, which are also involved in visual processing. CONCLUSIONS: A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability observed in migraineurs. The finding in patients with both MWA and MWoA of thickness abnormalities in area V3A, previously described as a source in spreading changes involved in visual aura, raises the question as to whether a "silent" cortical spreading depression develops as well in MWoA. In addition, these experimental data may provide clinicians and researchers with a noninvasively acquirable migraine biomarker.

White matter abnormalities in dystonia normalize after botulinum toxin treatment.

The pathophysiology of dystonia is still poorly understood. We used diffusion tensor imaging to screen for white matter abnormalities in regions between the basal ganglia and the thalamus in cervical and hand dystonia patients. All patients exhibited an abnormal hemispheric asymmetry in a focal region between the pallidum and the thalamus. This asymmetry was absent 4 weeks after the same patients were treated with intramuscular botulinum toxin injections. These findings represent a new systems-level abnormality in dystonia, which may lead to new insights about the pathophysiology of movement disorders. More generally, these findings demonstrate central nervous system changes following peripheral reductions in muscle activity. This raises the possibility that we have observed activity-dependent white matter plasticity in the adult human brain.

Influence of anisotropic conductivity on EEG source reconstruction: investigations in a rabbit model.

The aim of our work was to quantify the influence of white matter anisotropic conductivity information on electroencephalography (EEG) source reconstruction. We performed this quantification in a rabbit head using both simulations and source localization based on invasive measurements. In vivo anisotropic (tensorial) conductivity information was obtained from magnetic resonance diffusion tensor imaging and included into a high-resolution finite-element model. When neglecting anisotropy in the simulations, we found a shift in source location of up to 1.3 mm with a mean value of 0.3 mm. The averaged orientational deviation was 10 degree and the mean magnitude error of the dipole was 29%. Source localization of the first cortical components after median and tibial nerve stimulation resulted in anatomically verified dipole positions with no significant anisotropy effect. Our results indicate that the expected average source localization error due to anisotropic white matter conductivity is within the principal accuracy limits of current inverse procedures. However, larger localization errors might occur in certain cases. In contrast, dipole orientation and dipole strength are influenced significantly by the anisotropy. We conclude that the inclusion of tissue anisotropy information improves source estimation procedures.

White matter alterations in cerebral amyloid angiopathy measured by diffusion tensor imaging.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) represents beta-amyloid deposition in the small- and medium-sized vessels of the brain and meninges. CAA contributes to altered vessel function and is associated with white matter damage, cognitive impairment, and most salient, hemorrhagic stroke. We used diffusion tensor imaging to evaluate the anatomic distribution of white matter degeneration in participants diagnosed with advanced CAA. METHODS: Diffusion tensor imaging was obtained from 11 participants diagnosed with CAA-related intracerebral hemorrhage and 13 matched healthy control participants. Fractional anisotropy (FA) and diffusivity maps were compared using voxel based t test and region-of-interest analyses. RESULTS: FA was reduced in CAA in temporal white matter and in the splenium of the corpus callosum (P<0.001 with approximately 17% reduction in temporal white matter and 15% reduction in the splenium). FA was marginally increased in CAA in the posterior limb of the internal capsule and subthalamic gray matter regions (approximately 7% increase in subthalamic gray). FA changes were bilateral, remained significant in cluster analysis controlling for multiple comparisons, and did not depend on the hemisphere of the cerebral hemorrhage. Diffusivity was not substantially altered. CONCLUSIONS: These findings suggest that a pattern of regional brain tissue degeneration is a characteristic feature of advanced CAA.