Dennis P. Hanson

Subtraction ictal SPECT co‐registered to MRI improves clinical usefulness of SPECT in localizing the surgical seizure focus

Traditional side-by-side visual interpretation of ictal and interictal single-photon emission computed tomography (SPECT) scans can be difficult in identifying the surgical focus, particularly in patients with extratemporal or otherwise unlocalized intractable epilepsy. Computer-aided subtraction ictal SPECT co-registered to MRI (SISCOM) may improve the clinical usefulness of SPECT in localizing the surgical seizure focus. We studied 51 consecutive intractable partial epilepsy patients who had interictal and ictal scans. The SPECT studies were blindly reviewed and classified as either localizing to 1 of 16 sites in the brain or as nonlocalizing. SISCOM images were localizing in 45 of 51 (88.2%) compared with 20 of 51 (39.2%) for traditional side-by-side inspection of ictal and interictal SPECT images (p < 0.0001). Inter-rater agreement for two independent reviewers was better for SISCOM (84.3% versus 41.2%, K = 0.83 versus 0.26; p < 0.0001). Concordance of seizure localization with the more established tests was also higher for SISCOM. Late injection of the radiotracer (>45 seconds), but not secondary generalization of the seizure, was associated with a falsely localizing or nonlocalizing SISCOM. Epilepsy surgery patients whose SISCOM localization was concordant with the surgical site were more likely to have excellent outcome than patients with nonconcordant or nonlocalizing findings (62.5% [10/16] versus 20% [2/10]; p < 0.05). On the other hand, seizure localization by the traditional method of SPECT inspection had no significant association with postsurgical outcome. We conclude that SISCOM improves the sensitivity and the specificity of SPECT in localizing the seizure focus for epilepsy surgery. Concordance between SISCOM localization and site of surgery is predictive of postsurgical improvement in seizure outcome.

Subtraction ictal SPET co-registered to mri in partial epilepsy : Description and technical validation of the method with phantom and patient studies

Computer-aided subtraction of the co-registered and normalized interictal from the ictal single photon emission tomography (SPET) scan, followed by co-registration to the magnetic resonance image, may improve the utility of ictal SPET in the localization of partial epilepsy. This paper describes and technically validates our method. The SPET to SPET co-registration was tested using six sequential 99Tcm brain phantom SPET images of different known positions (15 matches). The registration error was determined by multiplying the calculated match transformation matrix by the inverse of the known transformation matrix. The ‘worst case’ co-registration error was less that one voxel diameter in all cases (median 3.2 mm, range 1.2–4.8 mm). For interictal to ictal SPET registrations in 10 consecutive intractable partial epilepsy patients, a similar root mean square distance (RMSD) between corresponding points on the matched scans was found as for the phantom studies (median 2.2 vs 2.6 mm). The appropriateness of our normalization was studied by comparing the pixel intensity distributions between the matched scans, and by analysing the subtraction pixel intensity distribution. The pixel intensity distribution for both the normalized phantom, and paired normalized patient studies, were closely matched to each other except for the extreme values, which in clinical situations likely represent regions of ictal activation or depression. The subtraction image intensity distributions were symmetrically centred on zero for all values up to at least within the 5th to 95th centile range, confirming good normalization for the ‘non-activated’ pixels. Also, a linear relationship was demonstrated between the measured pixel intensity on the phantom scans and the true changes in 99Tcm activity based on its decay constant. The results of this study demonstrate that our method produces accurate SPET to SPET co-registration, and appropriate SPET normalization, thereby allowing a valid ictal subtraction image to be derived.

A human antibody that promotes remyelination enters the CNS and decreases lesion load as detected by T2-weighted spinal cord MRI in a virus-induced murine model of MS

The human monoclonal antibody rHIgM22 enhances remyelination following spinal cord demyelination in a virus‐induced murine model of multiple sclerosis. Using three‐dimensional T2‐weighted in vivo spinal cord magnetic resonance imaging (MRI), we have therefore assessed the extent of spinal cord demyelination, before and after 5 weeks of treatment with rHIgM22, to determine whether antibody enhanced remyelination can be detected by MRI. A significant decrease was seen in T2 high signal lesion volume following antibody treatment. Histologic examination of the spinal cord tissue reveals that this decrease in lesion volume correlates with antibody promoted remyelination. To show that rHIgM22 enters the spinal cord and colocalizes with demyelinating lesions, we used ultrasmall superparamagnetic iron oxide particle (USPIO)‐labeled antibodies. This may be considered as additional evidence to the hypothesis that rHIgM22 promotes remyelination by local effects in the lesions, likely by binding to CNS cells. The reduction in high signal T2‐weighted lesion volume may be an important outcome measure in future clinical trials in humans.

Mapping High-Fidelity Volume Rendering for Medical Imaging to CPU, GPU and Many-Core Architectures

Medical volumetric imaging requires high fidelity, high performance rendering algorithms. We motivate and analyze new volumetric rendering algorithms that are suited to modern parallel processing architectures. First, we describe the three major categories of volume rendering algorithms and confirm through an imaging scientist-guided evaluation that ray-casting is the most acceptable. We describe a thread- and data-parallel implementation of ray-casting that makes it amenable to key architectural trends of three modern commodity parallel architectures: multi-core, GPU, and an upcoming many-core Intelreg architecture code-named Larrabee. We achieve more than an order of magnitude performance improvement on a number of large 3D medical datasets. We further describe a data compression scheme that significantly reduces data-transfer overhead. This allows our approach to scale well to large numbers of Larrabee cores.

Statistical SPECT processing in MRI-negative epilepsy surgery

Objective: To evaluate the benefit of statistical SPECT processing over traditional subtraction methods, we compared ictal–interictal SPECT analyzed by statistical parametric mapping (SPM) (ISAS), statistical ictal SPECT coregistered to MRI (STATISCOM), and subtraction ictal–interictal SPECT coregistered with MRI (SISCOM) in patients with MRI-negative focal temporal lobe epilepsy (nTLE) and extratemporal lobe epilepsy (nETLE). Methods: We retrospectively identified 49 consecutive cases of drug-resistant focal epilepsy that had a negative preoperative MRI and underwent interictal and ictal SPECT prior to resective epilepsy surgery. Interictal and ictal SPECT scans were analyzed using SISCOM, ISAS, and STATISCOM to create hyperperfusion and hypoperfusion maps for each patient. Reviewers blinded to clinical data and the SPECT analysis method marked the site of probable seizure origin and indicated their confidence in the localization. Results: In nTLE and nETLE, the hyperperfusions detected by STATISCOM (71% nTLE, 57% nETLE) and ISAS (67% nTLE, 53% nETLE) were more often colocalized with surgery resection site compared to SISCOM (38% nTLE, 36% nETLE). In nTLE, localization of the hyperperfusion to the region of surgery was associated with an excellent outcome for STATISCOM (p = 0.005) and ISAS (p = 0.027), but not in SISCOM (p = 0.071). This association was not present in nETLE for any method. Conclusion: In an unselected group of patients with normal MRI and focal epilepsy, SPM-based methods of SPECT processing showed better localization of SPECT hyperperfusion to surgical resection site and higher interobserver agreement compared to SISCOM. These results show the benefit of statistical SPECT processing methods and further highlight the challenge of nETLE.

Rezūm System Water Vapor Treatment for Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: Validation of Convective Thermal Energy Transfer and Characterization With Magnetic Resonance Imaging and 3-Dimensional Renderings.

OBJECTIVE To evaluate by magnetic resonance imaging the physical effects of convective thermal energy transfer with water vapor as a means of treating lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS Sixty-five men with lower urinary tract symptoms were treated with the Rezūm System by transurethral intraprostatic injection of water vapor. A group of 45 of these men consented to undergo a series of gadolinium-enhanced magnetic resonance imagings of the prostate after treatment to monitor the size and location of ablative lesions, their time course of resolution, and the corresponding change in prostate tissue volume. Visualization was conducted at 1 week, 1, 3, and 6 months after treatment. RESULTS Outcomes were available for 44 patients. Convective thermal lesions were limited to the transition zone and correlated with targeted treatment locations. At 1 week after treatment, the mean volume of ablative lesions was 8.2 cm(3) (0.5-24.0 cm(3)). At 6 months, whole prostate volume was reduced by a mean of 28.9% and transition zone volume by 38.0% as compared with baseline 1-week images. At 3 and 6 months after treatment, the lesion volumes had reduced by 91.5% and 95.1%, respectively. Lesions remained within the targeted treatment zone without compromising integrity of the bladder, rectum, or striated urinary sphincter. CONCLUSION This imaging study confirms the delivery of convective water vapor technology to create thermal lesions in the prostate tissue. Lesions generated underwent near complete resolution by 3 and 6 months after treatment with a concomitant one-third reduction in overall prostate and transition zone volumes.

A workstation for multi-dimensional display and analysis of biomedical images

The capability to extract objective and quantitatively accurate information from 3-D radiographic biomedical images has not kept pace with the capabilities to produce the images themselves. This is rather an ironic paradox, since on the one hand the new 3-D and 4-D imaging capabilities promise significant potential for providing greater specificity and sensitivity (i.e. precise objective discrimination and accurate quantitative measurement of body tissue characteristics and function) in clinical diagnostic and basic investigative imaging procedures than ever possible before, but on the other hand, the momentous advances in computer and associated electronic imaging technology which have made these 3-D imaging capabilities possible have not been concomitantly developed for full exploitation of these capabilities. Therefore, we have developed a powerful new microcomputer-based system which permits detailed investigations and evaluation of 3-D and 4-D (dynamic 3-D) biomedical images. The system comprises a special workstation to which all the information in a large 3-D image data base is accessible for rapid display, manipulation, and measurement. The system provides important capabilities for simultaneously representing and analyzing both structural and functional data and their relationships in various organs of the body. This paper provides a detailed description of this system, as well as some of the rationale, background, theoretical concepts, and practical considerations related to system implementation.

Progressive Brain Atrophy in Super-refractory Status Epilepticus

Importance Prolonged seizures in super-refractory status epilepticus (SRSE) have been shown to cause neuronal death and reorganization, and visual inspection in individual case studies has demonstrated progressive cortical and subcortical atrophy. At present, magnetic resonance imaging (MRI) studies that evaluate brain atrophy in SRSE are lacking. Objectives To document and quantify the development of atrophy over time in SRSE. Design, Setting, and Participants This retrospective medical record review included all patients with SRSE who were admitted to a tertiary referral campus of the Mayo Clinic Hospital with SRSE from January 1, 2001, to December 31, 2013. Patients with (1) an initial MRI scan performed within 2 weeks of SRSE onset, (2) a second MRI scan within 6 months of SRSE resolution, and (3) a minimum duration of 1 week between MRI scans were included. The ventricular brain ratio (VBR) was measured on T2-weighted fluid-attenuated inversion recovery (FLAIR) images at disease onset and during follow-up. Measurements were performed on axial FLAIR images with section thickness of less than 5 mm. The plane immediately superior to the caudate head was chosen for analysis. The hypothesis that atrophy develops during SRSE despite seizure control (electroencephalogram background suppression with anesthetic drugs) was tested. Data were analyzed from June 1 to December 31, 2015. Main Outcomes and Measures Change in VBR (ΔVBR) as a percentage of the starting measure. Results Nineteen patients met the inclusion criteria; these included 10 men (53%) and 9 women (47%) with a median age of 41 (interquartile range [IQR], 25-68) years. Anesthetic agents were required for a median of 13 (IQR, 5-37) days. Initial MRI was performed a median of 2 (IQR, 1-7.5) days from the onset of SRSE, and the second MRI was performed a median of 11 (IQR, 5-15.5) days from the resolution of SRSE, with a median of 40 (IQR, 15-65) days between MRI scans. Median ΔVBR was 23.3% (IQR, 10.5%-70.3%). A significant correlation between the duration of anesthetic agent use and ΔVBR was found (Spearman r = 0.54; P = .02). Conclusions and Relevance Atrophy developed in all patients with SRSE who underwent serial imaging, despite administration of agents for seizure control. The degree of atrophy appears to be related to the duration of SRSE.

Analysis of Brain SPECT Images Coregistered with MRI in Patients with Epilepsy: Comparison of Three Methods: SPECT/MRI for Seizure Localization

SISCOM and STATISCOM were clinically proved to be effective for ictal/inter‐ictal single‐photon emission computed tomography (SPECT) analysis coregistered with magnetic resonance imaging (MRI) for seizure localization. Recently, a software package also became available for this analysis. This study aimed to investigate and compare the performance of these analysis methods for seizure localization.

Quantitative characterization of brain β-amyloid in 718 normal subjects using a joint PiB/FDG PET image histogram

We have previously described an automated system for the co-registration of PiB and FDG PET images with structural MRI and a neurological anatomy atlas to produce region-specific quantization of cortical activity and amyloid burden. We also reported a global joint PiB/FDG histogram-based measure (FDG-Associated PiB Uptake Ratio – FAPUR) that performed as well as regional PiB ratio in stratifying Alzheimer’s disease (AD) and Lewy Body Dementia (LBD) patients from normal subjects in an autopsy-verified cohort of 31. In this paper we examine results of this analysis on a clinically-verified cohort of 718 normal volunteers. We found that the global FDG ratio correlated negatively with age (r2 = 0.044) and global PiB ratio correlated positively with age (r2=0.038). FAPUR also correlated negatively with age (r2-.025), and in addition, we introduce a new metric – the Pearson’s correlation coefficient (r2) of the joint PiB/FDG histogram which correlates positively (r2=0.014) with age. We then used these measurements to construct age-weighted Z-scores for all measurements made on the original autopsy cohort. We found similar stratification using Z-scores compared to raw values; however, the joint PiB/FDG r2 Z-score showed the greatest stratification ability.