Publications

2016
Fatih Incekara, Olutayo Olubiyi, Aysegul Ozdemir, Tom Lee, Laura Rigolo, and Alexandra Golby. 2016. “The Value of Pre- and Intraoperative Adjuncts on the Extent of Resection of Hemispheric Low-Grade Gliomas: A Retrospective Analysis.” J Neurol Surg A Cent Eur Neurosurg, 77, 2, Pp. 79-87.Abstract

Background To achieve maximal resection with minimal risk of postoperative neurologic morbidity, different neurosurgical adjuncts are being used during low-grade glioma (LGG) surgery. Objectives To investigate the effect of pre- and intraoperative adjuncts on the extent of resection (EOR) of hemispheric LGGs. Methods Medical records were reviewed to identify patients of any sex, ≥ 18 years of age, who underwent LGG surgery at X Hospital between January 2005 and July 2013. Patients were divided into eight subgroups based on the use of various combinations of a neuronavigation system alone (NN), functional MRI-diffusion tensor imaging (fMRI-DTI) guided neuronavigation (FD), intraoperative MRI (MR), and direct electrical stimulation (DES). Initial and residual tumors were measured, and mean EOR was compared between groups. Results Of all 128 patients, gross total resection was achieved in 23.4%. Overall mean EOR was 81.3% ± 20.5%. Using DES in combination with fMRI-DTI (mean EOR: 86.7% ± 12.4%) on eloquent tumors improved mean EOR significantly after adjustment for potential confounders when compared with NN alone (mean EOR: 76.4% ± 25.5%; p = 0.001). Conclusions Using DES in combination with fMRI and DTI significantly improves EOR when LGGs are located in eloquent areas compared with craniotomies in which only NN was used.

2015
Nathan C Himes, Thanissara Chansakul, and Thomas C Lee. 2015. “Magnetic Resonance Imaging-Guided Spine Interventions.” Magn Reson Imaging Clin N Am, 23, 4, Pp. 523-32.Abstract
MR imaging-guided interventions for treatment of low back pain and for diagnosis and treatment of soft tissue and bony spinal lesions have been shown to be feasible, effective, and safe. Advantages of this technique include the absence of ionizing radiation, the high tissue contrast, and multiplanar imaging options. Recent advancements in MR imaging systems allow improved image qualities and real-time guidance. One exciting application is MR imaging-guided cryotherapy of spinal lesions, including treating such lesions as benign osteoid osteomas and malignant metastatic disease in patients who are not good surgical candidates. This particular technique shows promise for local tumor control and pain relief in appropriate patients.
Hao Su, Weijian Shang, Gregory Cole, Gang Li, Kevin Harrington, Alexander Camilo, Junichi Tokuda, Clare M Tempany, Nobuhiko Hata, and Gregory S Fischer. 2015. “Piezoelectrically Actuated Robotic System for MRI-Guided Prostate Percutaneous Therapy.” IEEE ASME Trans Mechatron, 20, 4, Pp. 1920-1932.Abstract
This paper presents a fully-actuated robotic system for percutaneous prostate therapy under continuously acquired live magnetic resonance imaging (MRI) guidance. The system is composed of modular hardware and software to support the surgical workflow of intra-operative MRI-guided surgical procedures. We present the development of a 6-degree-of-freedom (DOF) needle placement robot for transperineal prostate interventions. The robot consists of a 3-DOF needle driver module and a 3-DOF Cartesian motion module. The needle driver provides needle cannula translation and rotation (2-DOF) and stylet translation (1-DOF). A custom robot controller consisting of multiple piezoelectric motor drivers provides precision closed-loop control of piezoelectric motors and enables simultaneous robot motion and MR imaging. The developed modular robot control interface software performs image-based registration, kinematics calculation, and exchanges robot commands and coordinates between the navigation software and the robot controller with a new implementation of the open network communication protocol OpenIGTLink. Comprehensive compatibility of the robot is evaluated inside a 3-Tesla MRI scanner using standard imaging sequences and the signal-to-noise ratio (SNR) loss is limited to 15%. The image deterioration due to the present and motion of robot demonstrates unobservable image interference. Twenty-five targeted needle placements inside gelatin phantoms utilizing an 18-gauge ceramic needle demonstrated 0.87 mm root mean square (RMS) error in 3D Euclidean distance based on MRI volume segmentation of the image-guided robotic needle placement procedure.
Vilmos Kertesz, David Calligaris, Daniel R Feldman, Armen Changelian, Edward R Laws, Sandro Santagata, Nathalie YR Agar, and Gary J Van Berkel. 2015. “Profiling of Adrenocorticotropic Hormone and Arginine Vasopressin in Human Pituitary Gland and Tumor Thin Tissue Sections using Droplet-based Liquid-microjunction Surface-sampling-HPLC-ESI-MS-MS.” Anal Bioanal Chem, 407, 20, Pp. 5989-98.Abstract

Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections, using a fully automated droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS system for spatially resolved sampling, HPLC separation, and mass spectrometric detection. Excellent correlation was found between the protein distribution data obtained with this method and data obtained with matrix-assisted laser desorption/ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis), and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH-secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH-secreting adenomas and in normal anterior adenohypophysis compared with non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis, as expected. This work reveals that a fully automated droplet-based liquid-microjunction surface-sampling system coupled to HPLC-ESI-MS-MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, including AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity, and specificity of this method support the potential of this basic technology, with further advancement, for assisting surgical decision-making. Graphical Abstract Mass spectrometry based profiling of hormones in human pituitary gland and tumor thin tissue sections.

Lipeng Ning, Frederik Laun, Yaniv Gur, Edward VR DiBella, Samuel Deslauriers-Gauthier, Thinhinane Megherbi, Aurobrata Ghosh, Mauro Zucchelli, Gloria Menegaz, Rutger Fick, Samuel St-Jean, Michael Paquette, Ramon Aranda, Maxime Descoteaux, Rachid Deriche, Lauren O'Donnell, and Yogesh Rathi. 2015. “Sparse Reconstruction Challenge for Diffusion MRI: Validation on a Physical Phantom to Determine which Acquisition Scheme and Analysis Method to use?” Med Image Anal, 26, 1, Pp. 316-31.Abstract

Diffusion magnetic resonance imaging (dMRI) is the modality of choice for investigating in-vivo white matter connectivity and neural tissue architecture of the brain. The diffusion-weighted signal in dMRI reflects the diffusivity of water molecules in brain tissue and can be utilized to produce image-based biomarkers for clinical research. Due to the constraints on scanning time, a limited number of measurements can be acquired within a clinically feasible scan time. In order to reconstruct the dMRI signal from a discrete set of measurements, a large number of algorithms have been proposed in recent years in conjunction with varying sampling schemes, i.e., with varying b-values and gradient directions. Thus, it is imperative to compare the performance of these reconstruction methods on a single data set to provide appropriate guidelines to neuroscientists on making an informed decision while designing their acquisition protocols. For this purpose, the SPArse Reconstruction Challenge (SPARC) was held along with the workshop on Computational Diffusion MRI (at MICCAI 2014) to validate the performance of multiple reconstruction methods using data acquired from a physical phantom. A total of 16 reconstruction algorithms (9 teams) participated in this community challenge. The goal was to reconstruct single b-value and/or multiple b-value data from a sparse set of measurements. In particular, the aim was to determine an appropriate acquisition protocol (in terms of the number of measurements, b-values) and the analysis method to use for a neuroimaging study. The challenge did not delve on the accuracy of these methods in estimating model specific measures such as fractional anisotropy (FA) or mean diffusivity, but on the accuracy of these methods to fit the data. This paper presents several quantitative results pertaining to each reconstruction algorithm. The conclusions in this paper provide a valuable guideline for choosing a suitable algorithm and the corresponding data-sampling scheme for clinical neuroscience applications.

Gaurie Tilak, Kemal Tuncali, Sang-Eun Song, Junichi Tokuda, Olutayo Olubiyi, Fiona Fennessy, Andriy Fedorov, Tobias Penzkofer, Clare M Tempany, and Nobuhiko Hata. 2015. “3T MR-guided in-bore Transperineal Prostate Biopsy: A Comparison of Robotic and Manual Needle-guidance Templates.” J Magn Reson Imaging, 42, 1, Pp. 63-71.Abstract

PURPOSE: To demonstrate the utility of a robotic needle-guidance template device as compared to a manual template for in-bore 3T transperineal magnetic resonance imaging (MRI)-guided prostate biopsy. MATERIALS AND METHODS: This two-arm mixed retrospective-prospective study included 99 cases of targeted transperineal prostate biopsies. The biopsy needles were aimed at suspicious foci noted on multiparametric 3T MRI using manual template (historical control) as compared with a robotic template. The following data were obtained: the accuracy of average and closest needle placement to the focus, histologic yield, percentage of cancer volume in positive core samples, complication rate, and time to complete the procedure. RESULTS: In all, 56 cases were performed using the manual template and 43 cases were performed using the robotic template. The mean accuracy of the best needle placement attempt was higher in the robotic group (2.39 mm) than the manual group (3.71 mm, P < 0.027). The mean core procedure time was shorter in the robotic (90.82 min) than the manual group (100.63 min, P < 0.030). Percentage of cancer volume in positive core samples was higher in the robotic group (P < 0.001). Cancer yields and complication rates were not statistically different between the two subgroups (P = 0.557 and P = 0.172, respectively). CONCLUSION: The robotic needle-guidance template helps accurate placement of biopsy needles in MRI-guided core biopsy of prostate cancer.

Chang-Sheng Mei, Renxin Chu, W. Scott Hoge, Lawrence P. Panych, and Bruno Madore. 2015. “Accurate Field Mapping in the Presence of B0 Inhomogeneities, Applied to MR Thermometry.” Magn Reson Med, 73, 6, Pp. 2142-51.Abstract

PURPOSE: To describe how B0 inhomogeneities can cause errors in proton resonance frequency (PRF) shift thermometry, and to correct for these errors. METHODS: With PRF thermometry, measured phase shifts are converted into temperature measurements through the use of a scaling factor proportional to the echo time, TE. However, B0 inhomogeneities can deform, spread, and translate MR echoes, potentially making the "true" echo time vary spatially within the imaged object and take on values that differ from the prescribed TE value. Acquisition and reconstruction methods able to avoid or correct for such errors are presented. RESULTS: Tests were performed in a gel phantom during sonication, and temperature measurements were made with proper shimming as well as with intentionally introduced B0 inhomogeneities. Errors caused by B0 inhomogeneities were observed, described, and corrected by the proposed methods. No statistical difference was found between the corrected results and the reference results obtained with proper shimming, while errors by more than 10% in temperature elevation were corrected for. The approach was also applied to an abdominal in vivo dataset. CONCLUSION: Field variations induce errors in measured field values, which can be detected and corrected. The approach was validated for a PRF thermometry application.

Xinyang Liu, Kemal Tuncali, William M Wells III, and Gary P. Zientara. 2015. “Automatic Iceball Segmentation with Adapted Shape Priors for MRI-guided Cryoablation.” J Magn Reson Imaging, 41, 2, Pp. 517-24.Abstract

PURPOSE: To develop and evaluate an automatic segmentation method that extracts the 3D configuration of the ablation zone, the iceball, from images acquired during the freezing phase of MRI-guided cryoablation. MATERIALS AND METHODS: Intraprocedural images at 63 timepoints from 13 kidney tumor cryoablation procedures were examined retrospectively. The images were obtained using a 3 Tesla wide-bore MRI scanner and axial HASTE sequence. Initialized with semiautomatically localized cryoprobes, the iceball was segmented automatically at each timepoint using the graph cut (GC) technique with adapted shape priors. RESULTS: The average Dice Similarity Coefficients (DSC), compared with manual segmentations, were 0.88, 0.92, 0.92, 0.93, and 0.93 at 3, 6, 9, 12, and 15 min timepoints, respectively, and the average DSC of the total 63 segmentations was 0.92 ± 0.03. The proposed method improved the accuracy significantly compared with the approach without shape prior adaptation (P = 0.026). The number of probes involved in the procedure had no apparent influence on the segmentation results using our technique. The average computation time was 20 s, which was compatible with an intraprocedural setting. CONCLUSION: Our automatic iceball segmentation method demonstrated high accuracy and robustness for practical use in monitoring the progress of MRI-guided cryoablation.

Yi Lu, Cecil Yeung, Alireza Radmanesh, Robert Wiemann, Peter M Black, and Alexandra J Golby. 2015. “Comparative Effectiveness of Frame-Based, Frameless, and Intraoperative Magnetic Resonance Imaging–Guided Brain Biopsy Techniques.” World Neurosurg, 83, 3, Pp. 261-8.Abstract

OBJECTIVE: To compare the diagnostic yield and safety profiles of intraoperative magnetic resonance imaging (MRI)-guided needle brain biopsy with 2 traditional brain biopsy methods: frame-based and frameless stereotactic brain biopsy. METHODS: A retrospective analysis was performed of 288 consecutive needle brain biopsies in 277 patients undergoing stereotactic brain biopsy with any of the 3 biopsy methods at Brigham and Women's Hospital from 2000-2008. Variables including age, sex, history of radiation and previous surgery, pathology results, complications, and postoperative length of hospital stay were analyzed. RESULTS: Over the course of 8 years, 288 brain biopsies were performed. Of these, 253 (87.8%) biopsies yielded positive diagnostic tissue. Young age (<40 years old) and history of brain radiation or surgery were significant negative predictors for a positive biopsy diagnostic yield. Excluding patients with prior radiation or surgeries, no significant difference in diagnostic yield was detected among the 3 groups, with frame-based biopsies yielding 96.9%, frameless biopsies yielding 91.8%, and intraoperative MRI-guided needle biopsies yielding 89.9% positive diagnostic yield. Serious adverse events occurred 19 biopsies (6.6%). Intraoperative MRI-guided brain biopsies were associated with less serious adverse events and the shortest postoperative hospital stay. CONCLUSIONS: Frame-based, frameless stereotactic, and intraoperative MRI-guided brain needle biopsy techniques have comparable diagnostic yield for patients with no prior treatments (either radiation or surgery). Intraoperative MRI-guided brain biopsy is associated with fewer serious adverse events and shorter hospital stay.

Alireza Radmanesh, Amir A Zamani, Stephen Whalen, Yanmei Tie, Ralph O Suarez, and Alexandra J Golby. 2015. “Comparison of Seeding Methods for Visualization of the Corticospinal Tracts using Single Tensor Tractography.” Clin Neurol Neurosurg, 129, Pp. 44-9.Abstract

OBJECTIVES: To compare five different seeding methods to delineate hand, foot, and lip components of the corticospinal tract (CST) using single tensor tractography. METHODS: We studied five healthy subjects and 10 brain tumor patients. For each subject, we used five different seeding methods, from (1) cerebral peduncle (CP), (2) posterior limb of the internal capsule (PLIC), (3) white matter subjacent to functional MRI activations (fMRI), (4) whole brain and then selecting the fibers that pass through both fMRI and CP (WBF-CP), and (5) whole brain and then selecting the fibers that pass through both fMRI and PLIC (WBF-PLIC). Two blinded neuroradiologists rated delineations as anatomically successful or unsuccessful tractography. The proportions of successful trials from different methods were compared by Fisher's exact test. RESULTS: To delineate hand motor tract, seeding through fMRI activation areas was more effective than through CP (p<0.01), but not significantly different from PLIC (p>0.1). WBF-CP delineated hand motor tracts in a larger proportion of trials than CP alone (p<0.05). Similarly, WBF-PLIC depicted hand motor tracts in a larger proportion of trials than PLIC alone (p<0.01). Foot motor tracts were delineated in all trials by either PLIC or whole brain seeding (WBF-CP and WBF-PLIC). Seeding from CP or fMRI activation resulted in foot motor tract visualization in 87% of the trials (95% confidence interval: 60-98%). The lip motor tracts were delineated only by WBF-PLIC and in 36% of trials (95% confidence interval: 11-69%). CONCLUSIONS: Whole brain seeding and then selecting the tracts that pass through two anatomically relevant ROIs can delineate more plausible hand and lip motor tracts than seeding from a single ROI. Foot motor tracts can be successfully delineated regardless of the seeding method used.

Julien Oster, Raul Llinares, Stephen Payne, Zion Tsz Ho Tse, Ehud Jeruham Schmidt, and Gari D Clifford. 2015. “Comparison of Three Artificial Models of the Magnetohydrodynamic Effect on the Electrocardiogram.” Comput Methods Biomech Biomed Engin, 18, 13, Pp. 1400-17.Abstract

The electrocardiogram (ECG) is often acquired during magnetic resonance imaging (MRI), but its analysis is restricted by the presence of a strong artefact, called magnetohydrodynamic (MHD) effect. MHD effect is induced by the flow of electrically charged particles in the blood perpendicular to the static magnetic field, which creates a potential of the order of magnitude of the ECG and temporally coincident with the repolarisation period. In this study, a new MHD model is proposed by using MRI-based 4D blood flow measurements made across the aortic arch. The model is extended to several cardiac cycles to allow the simulation of a realistic ECG acquisition during MRI examination and the quality assessment of MHD suppression techniques. A comparison of two existing models, based, respectively, on an analytical solution and on a numerical method-based solution of the fluids dynamics problem, is made with the proposed model and with an estimate of the MHD voltage observed during a real MRI scan. Results indicate a moderate agreement between the proposed model and the estimated MHD model for most leads, with an average correlation factor of 0.47. However, the results demonstrate that the proposed model provides a closer approximation to the observed MHD effects and a better depiction of the complexity of the MHD effect compared with the previously published models, with an improved correlation (+5%), coefficient of determination (+22%) and fraction of energy (+1%) compared with the best previous model. The source code will be made freely available under an open source licence to facilitate collaboration and allow more rapid development of more accurate models of the MHD effect.

Stan T Gregory, John Oshinski, Ehud J Schmidt, Raymond Y Kwong, William G Stevenson, and Zion Tsz Ho Tse. 2015. “Continuous Rapid Quantification of Stroke Volume Using Magnetohydrodynamic Voltages in 3T Magnetic Resonance Imaging.” Circ Cardiovasc Imaging, 8, 12.Abstract
BACKGROUND: To develop a technique to noninvasively estimate stroke volume in real time during magnetic resonance imaging (MRI)-guided procedures, based on induced magnetohydrodynamic voltages (VMHD) that occur in ECG recordings during MRI exams, leaving the MRI scanner free to perform other imaging tasks. Because of the relationship between blood flow (BF) and VMHD, we hypothesized that a method to obtain stroke volume could be derived from extracted VMHD vectors in the vectorcardiogram (VCG) frame of reference (VMHDVCG). METHODS AND RESULTS: To estimate a subject-specific BF-VMHD model, VMHDVCG was acquired during a 20-s breath-hold and calibrated versus aortic BF measured using phase-contrast magnetic resonance in 10 subjects (n=10) and 1 subject diagnosed with premature ventricular contractions. Beat-to-beat validation of VMHDVCG-derived BF was performed using real-time phase-contrast imaging in 7 healthy subjects (n=7) during 15-minute cardiac exercise stress tests and 30 minutes after stress relaxation in 3T MRIs. Subject-specific equations were derived to correlate VMHDVCG with BF at rest and validated using real-time phase-contrast. An average error of 7.22% and 3.69% in stroke volume estimation, respectively, was found during peak stress and after complete relaxation. Measured beat-to-beat BF time history derived from real-time phase-contrast and VMHD was highly correlated using a Spearman rank correlation coefficient during stress tests (0.89) and after stress relaxation (0.86). CONCLUSIONS: Accurate beat-to-beat stroke volume and BF were estimated using VMHDVCG extracted from intra-MRI 12-lead ECGs, providing a means to enhance patient monitoring during MR imaging and MR-guided interventions.
Lauren J O'Donnell and Ofer Pasternak. 2015. “Does Diffusion MRI Tell Us Anything about the White Matter? An Overview of Methods and Pitfalls.” Schizophr Res, 161, 1, Pp. 133-41.Abstract

One key pitfall in diffusion magnetic resonance imaging (dMRI) clinical neuroimaging research is the challenge of understanding and interpreting the results of a complex analysis pipeline. The sophisticated algorithms employed by the analysis software, combined with the relatively non-specific nature of many diffusion measurements, lead to challenges in interpretation of the results. This paper is aimed at an intended audience of clinical researchers who are learning about dMRI or trying to interpret dMRI results, and who may be wondering "Does dMRI tell us anything about the white matter?" We present a critical review of dMRI methods and measures used in clinical neuroimaging research, focusing on the most commonly used analysis methods and the most commonly reported measures. We describe important pitfalls in every section, and provide extensive references for the reader interested in more detail.

Sonia Pujol, William M Wells III, Carlo Pierpaoli, Caroline Brun, James Gee, Guang Cheng, Baba Vemuri, Olivier Commowick, Sylvain Prima, Aymeric Stamm, Maged Goubran, Ali Khan, Terry Peters, Peter Neher, Klaus H Maier-Hein, Yundi Shi, Antonio Tristan-Vega, Gopalkrishna Veni, Ross Whitaker, Martin Styner, Carl-Fredrik Westin, Sylvain Gouttard, Isaiah Norton, Laurent Chauvin, Hatsuho Mamata, Guido Gerig, Arya Nabavi, Alexandra Golby, and Ron Kikinis. 2015. “The DTI Challenge: Toward Standardized Evaluation of Diffusion Tensor Imaging Tractography for Neurosurgery.” J Neuroimaging, 25, 6, Pp. 875-82.Abstract

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) tractography reconstruction of white matter pathways can help guide brain tumor resection. However, DTI tracts are complex mathematical objects and the validity of tractography-derived information in clinical settings has yet to be fully established. To address this issue, we initiated the DTI Challenge, an international working group of clinicians and scientists whose goal was to provide standardized evaluation of tractography methods for neurosurgery. The purpose of this empirical study was to evaluate different tractography techniques in the first DTI Challenge workshop. METHODS: Eight international teams from leading institutions reconstructed the pyramidal tract in four neurosurgical cases presenting with a glioma near the motor cortex. Tractography methods included deterministic, probabilistic, filtered, and global approaches. Standardized evaluation of the tracts consisted in the qualitative review of the pyramidal pathways by a panel of neurosurgeons and DTI experts and the quantitative evaluation of the degree of agreement among methods. RESULTS: The evaluation of tractography reconstructions showed a great interalgorithm variability. Although most methods found projections of the pyramidal tract from the medial portion of the motor strip, only a few algorithms could trace the lateral projections from the hand, face, and tongue area. In addition, the structure of disagreement among methods was similar across hemispheres despite the anatomical distortions caused by pathological tissues. CONCLUSIONS: The DTI Challenge provides a benchmark for the standardized evaluation of tractography methods on neurosurgical data. This study suggests that there are still limitations to the clinical use of tractography for neurosurgical decision making.

Muna Aryal, Juyoung Park, Natalia Vykhodtseva, Yong-Zhi Zhang, and Nathan McDannold. 2015. “Enhancement in Blood-Tumor Barrier Permeability and Delivery of Liposomal Doxorubicin using Focused Ultrasound and Microbubbles: Evaluation during Tumor Progression in a Rat Glioma Model.” Phys Med Biol, 60, 6, Pp. 2511-27.Abstract

Effective drug delivery to brain tumors is often challenging because of the heterogeneous permeability of the 'blood tumor barrier' (BTB) along with other factors such as increased interstitial pressure and drug efflux pumps. Focused ultrasound (FUS) combined with microbubbles can enhance the permeability of the BTB in brain tumors, as well as the blood-brain barrier in the surrounding tissue. In this study, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to characterize the FUS-induced permeability changes of the BTB in a rat glioma model at different times after implantation. 9L gliosarcoma cells were implanted in both hemispheres in male rats. At day 9, 14, or 17 days after implantation, FUS-induced BTB disruption using 690 kHz ultrasound and definity microbubbles was performed in one tumor in each animal. Before FUS, liposomal doxorubicin was administered at a dose of 5.67 mg kg(-1). This chemotherapy agent was previously shown to improve survival in animal glioma models. The transfer coefficient Ktrans describing extravasation of the MRI contrast agent Gd-DTPA was measured via DCE-MRI before and after sonication. We found that tumor doxorubicin concentrations increased monotonically (823  ±  600, 1817  ±  732 and 2432  ±  448 ng g(-1)) in the control tumors at 9, 14 and 17 d. With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P < 0.05, P < 0.01, and P < 0.0001 at days 9, 14, and 17, respectively) and were greater than the control tumors by a factor of two or more (2222  ±  784, 3687  ±  796 and 5658  ±  821 ng g(-1)) regardless of the stage of tumor growth. The transfer coefficient Ktrans was significantly (P < 0.05) enhanced compared to control tumors only at day 9 but not at day 14 or 17. These results suggest that FUS-induced enhancements in tumor drug delivery are relatively consistent over time, at least in this tumor model. These results are encouraging for the use of large drug carriers, as they suggest that even large/late-stage tumors can benefit from FUS-induced drug enhancement. Corresponding enhancements in Ktrans were found to be variable in large/late-stage tumors and not significantly different than controls, perhaps reflecting the size mismatch between the liposomal drug (~100 nm) and Gd-DTPA (molecular weight: 938 Da; hydrodynamic diameter: ≃2 nm). It may be necessary to use a larger MRI contrast agent to effectively evaluate the sonication-induced enhanced permeabilization in large/late-stage tumors when a large drug carrier such as a liposome is used.

Wei Wang, Akila N Viswanathan, Antonio L Damato, Yue Chen, Zion Tse, Li Pan, Junichi Tokuda, Ravi T Seethamraju, Charles L Dumoulin, Ehud J Schmidt, and Robert A Cormack. 2015. “Evaluation of an Active Magnetic Resonance Tracking System for Interstitial Brachytherapy.” Med Phys, 42, 12, Pp. 7114.Abstract

PURPOSE: In gynecologic cancers, magnetic resonance (MR) imaging is the modality of choice for visualizing tumors and their surroundings because of superior soft-tissue contrast. Real-time MR guidance of catheter placement in interstitial brachytherapy facilitates target coverage, and would be further improved by providing intraprocedural estimates of dosimetric coverage. A major obstacle to intraprocedural dosimetry is the time needed for catheter trajectory reconstruction. Herein the authors evaluate an active MR tracking (MRTR) system which provides rapid catheter tip localization and trajectory reconstruction. The authors assess the reliability and spatial accuracy of the MRTR system in comparison to standard catheter digitization using magnetic resonance imaging (MRI) and CT. METHODS: The MRTR system includes a stylet with microcoils mounted on its shaft, which can be inserted into brachytherapy catheters and tracked by a dedicated MRTR sequence. Catheter tip localization errors of the MRTR system and their dependence on catheter locations and orientation inside the MR scanner were quantified with a water phantom. The distances between the tracked tip positions of the MRTR stylet and the predefined ground-truth tip positions were calculated for measurements performed at seven locations and with nine orientations. To evaluate catheter trajectory reconstruction, fifteen brachytherapy catheters were placed into a gel phantom with an embedded catheter fixation framework, with parallel or crossed paths. The MRTR stylet was then inserted sequentially into each catheter. During the removal of the MRTR stylet from within each catheter, a MRTR measurement was performed at 40 Hz to acquire the instantaneous stylet tip position, resulting in a series of three-dimensional (3D) positions along the catheter's trajectory. A 3D polynomial curve was fit to the tracked positions for each catheter, and equally spaced dwell points were then generated along the curve. High-resolution 3D MRI of the phantom was performed followed by catheter digitization based on the catheter's imaging artifacts. The catheter trajectory error was characterized in terms of the mean distance between corresponding dwell points in MRTR-generated catheter trajectory and MRI-based catheter digitization. The MRTR-based catheter trajectory reconstruction process was also performed on three gynecologic cancer patients, and then compared with catheter digitization based on MRI and CT. RESULTS: The catheter tip localization error increased as the MRTR stylet moved further off-center and as the stylet's orientation deviated from the main magnetic field direction. Fifteen catheters' trajectories were reconstructed by MRTR. Compared with MRI-based digitization, the mean 3D error of MRTR-generated trajectories was 1.5 ± 0.5 mm with an in-plane error of 0.7 ± 0.2 mm and a tip error of 1.7 ± 0.5 mm. MRTR resolved ambiguity in catheter assignment due to crossed catheter paths, which is a common problem in image-based catheter digitization. In the patient studies, the MRTR-generated catheter trajectory was consistent with digitization based on both MRI and CT. CONCLUSIONS: The MRTR system provides accurate catheter tip localization and trajectory reconstruction in the MR environment. Relative to the image-based methods, it improves the speed, safety, and reliability of the catheter trajectory reconstruction in interstitial brachytherapy. MRTR may enable in-procedural dosimetric evaluation of implant target coverage.

Ofer Pasternak, Carl-Fredrik Westin, Brian Dahlben, Sylvain Bouix, and Marek Kubicki. 2015. “The Extent of Diffusion MRI Markers of Neuroinflammation and White Matter Deterioration in Chronic Schizophrenia.” Schizophr Res, 161, 1, Pp. 113-8.Abstract

In a previous study we have demonstrated, using a novel diffusion MRI analysis called free-water imaging, that the early stages of schizophrenia are more likely associated with a neuroinflammatory response and less so with a white matter deterioration or a demyelination process. What is not known is how neuroinflammation and white matter deterioration change along the progression of the disorder. In this study we apply the free-water measures on a population of 29 chronic schizophrenia subjects and compare them with 25 matching controls. Our aim was to compare the extent of free-water imaging abnormalities in chronic subjects with the ones previously obtained for subjects at their first psychotic episode. We find that chronic subjects showed a limited extent of abnormal increase in the volume of the extracellular space, suggesting a less extensive neuroinflammatory response relative to patients at the onset of schizophrenia. At the same time, the chronic schizophrenia subjects had greater extent of reduced fractional anisotropy compared to the previous study, suggesting increased white matter deterioration along the progression of the disease. Our findings substantiate the role of neuroinflammation in the earlier stages of the disorder, and the effect of neurodegeneration that is worsening in the chronic phase.

Muhammad M Abd-El-Barr, Seth M Santos, Linda S Aglio, Geoffrey S Young, Srinivasan Mukundan, Alexandra J Golby, William B Gormley, and Ian F Dunn. 2015. “"Extraoperative" MRI (eoMRI) for Brain Tumor Surgery: Initial Results at a Single Institution.” World Neurosurg, 83, 6, Pp. 921-8.Abstract
BACKGROUND: There is accumulating evidence that extent of resection (EOR) in intrinsic brain tumor surgery prolongs overall survival (OS) and progression-free survival (PFS). One of the strategies to increase EOR is the use of intraoperative MRI (ioMRI); however, considerable infrastructure investment is needed to establish and maintain a sophisticated ioMRI. We report the preliminary results of an extraoperative (eoMRI) protocol, with a focus on safety, feasibility, and EOR in intrinsic brain tumor surgery. METHODS: Ten patients underwent an eoMRI protocol consisting of surgical resection in a conventional operating room followed by an immediate MRI in a clinical MRI scanner while the patient was still under anesthesia. If findings of the MRI suggested residual safely resectable tumor, the patient was returned to the operating room. A retrospective volumetric analysis was undertaken to investigate the percentage of tumor resected after first resection and if applicable, after further resection. RESULTS: Six of 10 (60%) patients were thought to require no further resection after eoMRI. The EOR in these patients was 97.8% ± 1.8%. In the 4 patients who underwent further resection, the EOR during the original surgery was 88.5% ± 9.5% (P = 0.04). There was an average of 10.1% more tumor removed between the first and second surgery. In 3 of 4 (75%) of patients who returned for further resection, gross total resection of tumor was achieved. CONCLUSION: An eoMRI protocol appears to be a safe and practical method to ensure maximum safe resections in patients with brain tumors and can be performed readily in all centers with MRI capabilities.
Matthew Toews, Christian Wachinger, Raul San Jose Estepar, and William M Wells III. 2015. “A Feature-Based Approach to Big Data Analysis of Medical Images.” Inf Process Med Imaging, 24, Pp. 339-50.Abstract

This paper proposes an inference method well-suited to large sets of medical images. The method is based upon a framework where distinctive 3D scale-invariant features are indexed efficiently to identify approximate nearest-neighbor (NN) feature matches-in O (log N) computational complexity in the number of images N. It thus scales well to large data sets, in contrast to methods based on pair-wise image registration or feature matching requiring O(N) complexity. Our theoretical contribution is a density estimator based on a generative model that generalizes kernel density estimation and K-nearest neighbor (KNN) methods.. The estimator can be used for on-the-fly queries, without requiring explicit parametric models or an off-line training phase. The method is validated on a large multi-site data set of 95,000,000 features extracted from 19,000 lung CT scans. Subject-level classification identifies all images of the same subjects across the entire data set despite deformation due to breathing state, including unintentional duplicate scans. State-of-the-art performance is achieved in predicting chronic pulmonary obstructive disorder (COPD) severity across the 5-category GOLD clinical rating, with an accuracy of 89% if both exact and one-off predictions are considered correct.

Junichi Tokuda, William Plishker, Meysam Torabi, Olutayo I Olubiyi, George Zaki, Servet Tatli, Stuart G Silverman, Raj Shekher, and Nobuhiko Hata. 2015. “Graphics Processing Unit-Accelerated Nonrigid Registration of MR Images to CT Images During CT-Guided Percutaneous Liver Tumor Ablations.” Acad Radiol, 22, 6, Pp. 722-33.Abstract
RATIONALE AND OBJECTIVES: Accuracy and speed are essential for the intraprocedural nonrigid magnetic resonance (MR) to computed tomography (CT) image registration in the assessment of tumor margins during CT-guided liver tumor ablations. Although both accuracy and speed can be improved by limiting the registration to a region of interest (ROI), manual contouring of the ROI prolongs the registration process substantially. To achieve accurate and fast registration without the use of an ROI, we combined a nonrigid registration technique on the basis of volume subdivision with hardware acceleration using a graphics processing unit (GPU). We compared the registration accuracy and processing time of GPU-accelerated volume subdivision-based nonrigid registration technique to the conventional nonrigid B-spline registration technique. MATERIALS AND METHODS: Fourteen image data sets of preprocedural MR and intraprocedural CT images for percutaneous CT-guided liver tumor ablations were obtained. Each set of images was registered using the GPU-accelerated volume subdivision technique and the B-spline technique. Manual contouring of ROI was used only for the B-spline technique. Registration accuracies (Dice similarity coefficient [DSC] and 95% Hausdorff distance [HD]) and total processing time including contouring of ROIs and computation were compared using a paired Student t test. RESULTS: Accuracies of the GPU-accelerated registrations and B-spline registrations, respectively, were 88.3 ± 3.7% versus 89.3 ± 4.9% (P = .41) for DSC and 13.1 ± 5.2 versus 11.4 ± 6.3 mm (P = .15) for HD. Total processing time of the GPU-accelerated registration and B-spline registration techniques was 88 ± 14 versus 557 ± 116 seconds (P < .000000002), respectively; there was no significant difference in computation time despite the difference in the complexity of the algorithms (P = .71). CONCLUSIONS: The GPU-accelerated volume subdivision technique was as accurate as the B-spline technique and required significantly less processing time. The GPU-accelerated volume subdivision technique may enable the implementation of nonrigid registration into routine clinical practice.

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