Publications

2016
Chen Z, Tie Y, Olubiyi O, Zhang F, Mehrtash A, Rigolo L, Kahali P, Norton I, Pasternak O, Rathi Y, et al. Corticospinal Tract Modeling for Neurosurgical Planning by Tracking through Regions of Peritumoral Edema and Crossing Fibers using Two-tensor Unscented Kalman Filter Tractography. Int J Comput Assist Radiol Surg. 2016.Abstract

PURPOSE: The aim of this study was to present a tractography algorithm using a two-tensor unscented Kalman filter (UKF) to improve the modeling of the corticospinal tract (CST) by tracking through regions of peritumoral edema and crossing fibers. METHODS: Ten patients with brain tumors in the vicinity of motor cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-T magnetic resonance imaging (MRI) including functional MRI (fMRI) and a diffusion-weighted data set with 31 directions. Fiber tracking was performed using both single-tensor streamline and two-tensor UKF tractography methods. A two-region-of-interest approach was used to delineate the CST. Results from the two tractography methods were compared visually and quantitatively. fMRI was applied to identify the functional fiber tracts. RESULTS: Single-tensor streamline tractography underestimated the extent of tracts running through the edematous areas and could only track the medial projections of the CST. In contrast, two-tensor UKF tractography tracked fanning projections of the CST despite peritumoral edema and crossing fibers. Based on visual inspection, the two-tensor UKF tractography delineated tracts that were closer to motor fMRI activations, and it was apparently more sensitive than single-tensor streamline tractography to define the tracts directed to the motor sites. The volume of the CST was significantly larger on two-tensor UKF than on single-tensor streamline tractography ([Formula: see text]). CONCLUSION: Two-tensor UKF tractography tracks a larger volume CST than single-tensor streamline tractography in the setting of peritumoral edema and crossing fibers in brain tumor patients.

Torcuator RG, Hulou MM, Chavakula V, Jolesz FA, Golby AJ. Intraoperative Real-time MRI-guided Stereotactic Biopsy Followed by Laser Thermal Ablation for Progressive Brain Metastases after Radiosurgery. J Clin Neurosci. 2016;24:68-73.Abstract

Stereotactic radiosurgery is one of the treatment options for brain metastases. However, there are patients who will progress after radiosurgery. One of the potential treatments for this subset of patients is laser ablation. Image-guided stereotactic biopsy is important to determine the histopathological nature of the lesion. However, this is usually based on preoperative, static images, which may affect the target accuracy during the actual procedure as a result of brain shift. We therefore performed real-time intraoperative MRI-guided stereotactic aspiration and biopsies on two patients with symptomatic, progressive lesions after radiosurgery followed immediately by laser ablation. The patients tolerated the procedure well with no new neurologic deficits. Intraoperative MRI-guided stereotactic biopsy followed by laser ablation is safe and accurate, providing real-time updates and feedback during the procedure.

2015
Tie Y, Rigolo L, Ozdemir Ovalioglu A, Olubiyi O, Doolin KL, Mukundan S, Golby AJ. A New Paradigm for Individual Subject Language Mapping: Movie-Watching fMRI. J Neuroimaging. 2015;25(5):710-20.Abstract

BACKGROUND: Functional MRI (fMRI) based on language tasks has been used in presurgical language mapping in patients with lesions in or near putative language areas. However, if patients have difficulty performing the tasks due to neurological deficits, it leads to unreliable or noninterpretable results. In this study, we investigate the feasibility of using a movie-watching fMRI for language mapping. METHODS: A 7-minute movie clip with contrasting speech and nonspeech segments was shown to 22 right-handed healthy subjects. Based on all subjects' language functional regions-of-interest, 6 language response areas were defined, within which a language response model (LRM) was derived by extracting the main temporal activation profile. Using a leave-one-out procedure, individuals' language areas were identified as the areas that expressed highly correlated temporal responses with the LRM derived from an independent group of subjects. RESULTS: Compared with an antonym generation task-based fMRI, the movie-watching fMRI generated language maps with more localized activations in the left frontal language area, larger activations in the left temporoparietal language area, and significant activations in their right-hemisphere homologues. Results of 2 brain tumor patients' movie-watching fMRI using the LRM derived from the healthy subjects indicated its ability to map putative language areas; while their task-based fMRI maps were less robust and noisier. CONCLUSIONS: These results suggest that it is feasible to use this novel "task-free" paradigm as a complementary tool for fMRI language mapping when patients cannot perform the tasks. Its deployment in more neurosurgical patients and validation against gold-standard techniques need further investigation.

Garlapati RR, Mostayed A, Joldes GR, Wittek A, Doyle B, Miller K. Towards Measuring Neuroimage Misalignment. Comput Biol Med. 2015;64:12-23.Abstract

To enhance neuro-navigation, high quality pre-operative images must be registered onto intra-operative configuration of the brain. Therefore evaluation of the degree to which structures may remain misaligned after registration is critically important. We consider two Hausdorff Distance (HD)-based evaluation approaches: the edge-based HD (EBHD) metric and the Robust HD (RHD) metric as well as various commonly used intensity-based similarity metrics such as Mutual Information (MI), Normalised Mutual Information (NMI), Entropy Correlation Coefficient (ECC), Kullback-Leibler Distance (KLD) and Correlation Ratio (CR). We conducted the evaluation by applying known deformations to simple sample images and real cases of brain shift. We conclude that the intensity-based similarity metrics such as MI, NMI, ECC, KLD and CR do not correlate well with actual alignment errors, and hence are not useful for assessing misalignment. On the contrary, the EBHD and the RHD metrics correlated well with actual alignment errors; however, they have been found to underestimate the actual misalignment. We also note that it is beneficial to present HD results as a percentile-HD curve rather than a single number such as the 95-percentile HD. Percentile-HD curves present the full range of alignment errors and also facilitate the comparison of results obtained using different approaches. Furthermore, the qualities that should be possessed by an ideal evaluation metric were highlighted. Future studies could focus on developing such an evaluation metric.

Chikarmane SA, Gombos EC, Jagadeesan J, Raut C, Jagannathan JP. MRI Findings of Radiation-associated Angiosarcoma of the Breast (RAS). J Magn Reson Imaging. 2015;42(3):763-70.Abstract

PURPOSE: To describe the magnetic resonance imaging (MRI) characteristics of radiation-associated breast angiosarcomas (RAS). MATERIALS AND METHODS: In this Institutional Review board (IRB)-approved retrospective study, 57 women were diagnosed with pathologically confirmed RAS during the study period (January 1999 to May 2013). Seventeen women underwent pretreatment breast MRI (prior to surgical resection or chemotherapy), of which 16 studies were available for review. Imaging features, including all available mammograms, ultrasounds, and breast MRIs, of these patients were evaluated by two radiologists independently and correlated with clinical management and outcomes. RESULTS: The median age of patients at original breast cancer diagnosis was 69.3 years (range 42-84 years), with average time from initial radiation therapy to diagnosis of RAS of 7.3 years (range 5.1-9.5 years). Nine women had mammograms (9/16, 56%) and six had breast ultrasound (US) (6/16, 38%) prior to MRI, which demonstrated nonsuspicious findings in 5/9 mammograms and 3/6 ultrasounds. Four patients had distinct intraparenchymal masses on mammogram and MRI. MRI findings included diffuse T2 high signal skin thickening (16/16, 100%). Nearly half (7/16, 44%) of patients had T2 low signal intensity lesions; all lesions rapidly enhanced on postcontrast T1 -weighted imaging. All women underwent surgical resection, with 8/16 (50%) receiving neoadjuvant chemotherapy. Four women died during the study period. CONCLUSION: Clinical, mammographic, and sonographic findings of RAS are nonspecific and may be occult on conventional breast imaging; MRI findings of RAS include rapidly enhancing dermal and intraparenchymal lesions, some of which are low signal on T2 weighted imaging.

Fennessy FM, Fedorov A, Penzkofer T, Kim KW, Hirsch MS, Vangel MG, Masry P, Flood TA, Chang M-C, Tempany CM, et al. Quantitative Pharmacokinetic Analysis of Prostate Cancer DCE-MRI at 3T: Comparison of Two Arterial Input Functions on Cancer Detection with Digitized Whole Mount Histopathological Validation. Magn Reson Imaging. 2015;33(7):886-94.Abstract
Accurate pharmacokinetic (PK) modeling of dynamic contrast enhanced MRI (DCE-MRI) in prostate cancer (PCa) requires knowledge of the concentration time course of the contrast agent in the feeding vasculature, the so-called arterial input function (AIF). The purpose of this study was to compare AIF choice in differentiating peripheral zone PCa from non-neoplastic prostatic tissue (NNPT), using PK analysis of high temporal resolution prostate DCE-MRI data and whole-mount pathology (WMP) validation. This prospective study was performed in 30 patients who underwent multiparametric endorectal prostate MRI at 3.0T and WMP validation. PCa foci were annotated on WMP slides and MR images using 3D Slicer. Foci ≥0.5cm(3) were contoured as tumor regions of interest (TROIs) on subtraction DCE (early-arterial - pre-contrast) images. PK analyses of TROI and NNPT data were performed using automatic AIF (aAIF) and model AIF (mAIF) methods. A paired t-test compared mean and 90th percentile (p90) PK parameters obtained with the two AIF approaches. Receiver operating characteristic (ROC) analysis determined diagnostic accuracy (DA) of PK parameters. Logistic regression determined correlation between PK parameters and histopathology. Mean TROI and NNPT PK parameters were higher using aAIF vs. mAIF (p<0.05). There was no significant difference in DA between AIF methods: highest for p90 volume transfer constant (K(trans)) (aAIF differences in the area under the ROC curve (Az) = 0.827; mAIF Az=0.93). Tumor cell density correlated with aAIF K(trans) (p=0.03). Our results indicate that DCE-MRI using both AIF methods is excellent in discriminating PCa from NNPT. If quantitative DCE-MRI is to be used as a biomarker in PCa, the same AIF method should be used consistently throughout the study.
Kato T, Okumura I, Song S-E, Golby AJ, Hata N. Tendon-Driven Continuum Robot for Endoscopic Surgery: Preclinical Development and Validation of a Tension Propagation Model. IEEE ASME Trans Mechatron. 2015;20(5):2252-2263.Abstract
In this paper, we present a tendon-driven continuum robot for endoscopic surgery. The robot has two sections for articulation actuated by tendon wires. By actuating the two sections independently, the robot can generate a variety of tip positions while maintaining the tip direction. This feature offers more flexibility in positioning the tip for large viewing angles of up to 180 degrees than does a conventional endoscope. To accurately estimate the tip position at large viewing angles, we employed kinematic mapping with a tension propagation model including friction between the tendon wires and the robot body. In a simulation study using this kinematic-mapping, the two-section robot at a target scale (outer diameter 1.7 mm and length 60 mm) produced a variety of tip positions within 50-mm ranges at the 180°-angle view. In the experimental validation, a 10:1 scale prototype performed three salient postures with different tip positions at the 180°-angle view. The proposed forward kinematic mapping (FKM) predicted the tip position within a tip-to-tip error of 6 mm over the 208-mm articulating length. The tip-to-tip error by FKM was significantly less than the one by conventional piecewise-constant-curvature approximation (PCCA) (FKM: 5.9 ± 2.9 mm vs. PCCA: 23.7 ± 3.6 mm, n=15, P < 0.01).
Balasubramanian M, Mulkern RV, Wells III WM, Sundaram P, Orbach DB. Magnetic Resonance Imaging of Ionic Currents in Solution: The Effect of Magnetohydrodynamic Flow. Magn Reson Med. 2015;74(4):1145-55.Abstract

PURPOSE: Reliably detecting MRI signals in the brain that are more tightly coupled to neural activity than blood-oxygen-level-dependent fMRI signals could not only prove valuable for basic scientific research but could also enhance clinical applications such as epilepsy presurgical mapping. This endeavor will likely benefit from an improved understanding of the behavior of ionic currents, the mediators of neural activity, in the presence of the strong magnetic fields that are typical of modern-day MRI scanners. THEORY: Of the various mechanisms that have been proposed to explain the behavior of ionic volume currents in a magnetic field, only one-magnetohydrodynamic flow-predicts a slow evolution of signals, on the order of a minute for normal saline in a typical MRI scanner. METHODS: This prediction was tested by scanning a volume-current phantom containing normal saline with gradient-echo-planar imaging at 3 T. RESULTS: Greater signal changes were observed in the phase of the images than in the magnitude, with the changes evolving on the order of a minute. CONCLUSION: These results provide experimental support for the MHD flow hypothesis. Furthermore, MHD-driven cerebrospinal fluid flow could provide a novel fMRI contrast mechanism.

Gombos EC, Jagadeesan J, Richman DM, Kacher DF. Magnetic Resonance Imaging-Guided Breast Interventions: Role in Biopsy Targeting and Lumpectomies. Magn Reson Imaging Clin N Am. 2015;23(4):547-61.Abstract
Contrast-enhanced breast MR imaging is increasingly being used to diagnose breast cancer and to perform biopsy procedures. The American Cancer Society has advised women at high risk for breast cancer to have breast MR imaging screening as an adjunct to screening mammography. This article places special emphasis on biopsy and operative planning involving MR imaging and reviews use of breast MR imaging in monitoring response to neoadjuvant chemotherapy. Described are peer-reviewed data on currently accepted MR imaging-guided procedures for addressing benign and malignant breast diseases, including intraoperative imaging.
Wang W. Magnetic Resonance-guided Active Catheter Tracking. Magn Reson Imaging Clin N Am. 2015;23(4):579-89.Abstract
Several advantages of MR imaging compared with other imaging modalities have provided the rationale for increased attention to MR-guided interventions, including its excellent soft tissue contrast, its capability to show both anatomic and functional information, and no use of ionizing radiation. An important aspect of MR-guided intervention is to provide visualization and navigation of interventional devices relative to the surrounding tissues. This article focuses on the methods for MR-guided active tracking in catheter-based interventions. Practical issues about implementation of active catheter tracking in a clinical setting are discussed and several current application examples are highlighted.
Pujol S, Wells III WM, Pierpaoli C, Brun C, Gee J, Cheng G, Vemuri B, Commowick O, Prima S, Stamm A, et al. The DTI Challenge: Toward Standardized Evaluation of Diffusion Tensor Imaging Tractography for Neurosurgery. J Neuroimaging. 2015;25(6):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.

Guo J, Huang HJ, Wang X, Wang W, Ellison H, Thomen RP, Gelman AE, Woods JC. Imaging Mouse Lung Allograft Rejection with (1) H MRI. Magn Reson Med. 2015;73(5):1970-8.Abstract

PURPOSE: To demonstrate that longitudinal, noninvasive monitoring via MRI can characterize acute cellular rejection in mouse orthotopic lung allografts. METHODS: Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig versus anti-CD4/anti-CD8 treated groups. A two-dimensional multislice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung at postoperative days 3, 7, and 14, just before sacrifice. Lung volume and parenchymal signal were measured, and lung compliance was calculated as volume change per pressure difference between high and low pressures. RESULTS: Normalized parenchymal signal in the control-Ig allograft increased over time, with statistical significance between day 14 and day 3 posttransplantation (0.046→0.789; P < 0.05), despite large intermouse variations; this was consistent with histopathologic evidence of rejection. Compliance of the control-Ig allograft decreased significantly over time (0.013→0.003; P < 0.05), but remained constant in mice treated with anti-CD4/anti-CD8 antibodies. CONCLUSION: Lung allograft rejection in individual mice can be monitored by lung parenchymal signal changes and by lung compliance through MRI. Longitudinal imaging can help us better understand the time course of individual lung allograft rejection and response to treatment.

Xu H, Lasso A, Fedorov A, Tuncali K, Tempany CM, Fichtinger G. Multi-slice-to-volume Registration for MRI-guided Transperineal Prostate Biopsy. Int J Comput Assist Radiol Surg. 2015;10(5):563-72.Abstract

PURPOSE: Prostate needle biopsy is a commonly performed procedure since it is the most definitive form of cancer diagnosis. Magnetic resonance imaging (MRI) allows target-specific biopsies to be performed. However, needle placements are often inaccurate due to intra-operative prostate motion and the lack of motion compensation techniques. This paper detects and determines the extent of tissue displacement during an MRI-guided biopsy so that the needle insertion plan can be adjusted accordingly. METHODS: A multi-slice-to-volume registration algorithm was developed to align the pre-operative planning image volume with three intra-operative orthogonal image slices of the prostate acquired immediately before needle insertion. The algorithm consists of an initial rigid transformation followed by a deformable step. RESULTS: A total of 14 image sets from 10 patients were studied. Based on prostate contour alignment, the registrations were accurate to within 2 mm. CONCLUSION: This algorithm can be used to increase the needle targeting accuracy by alerting the clinician if the biopsy target has moved significantly prior to needle insertion. The proposed method demonstrated feasibility of intra-operative target localization and motion compensation for MRI-guided prostate biopsy.

Li M, Miller K, Joldes GR, Doyle B, Garlapati RR, Kikinis R, Wittek A. Patient-specific Biomechanical Model as Whole-body CT Image Registration Tool. Med Image Anal. 2015;22(1):22-34.Abstract

Whole-body computed tomography (CT) image registration is important for cancer diagnosis, therapy planning and treatment. Such registration requires accounting for large differences between source and target images caused by deformations of soft organs/tissues and articulated motion of skeletal structures. The registration algorithms relying solely on image processing methods exhibit deficiencies in accounting for such deformations and motion. We propose to predict the deformations and movements of body organs/tissues and skeletal structures for whole-body CT image registration using patient-specific non-linear biomechanical modelling. Unlike the conventional biomechanical modelling, our approach for building the biomechanical models does not require time-consuming segmentation of CT scans to divide the whole body into non-overlapping constituents with different material properties. Instead, a Fuzzy C-Means (FCM) algorithm is used for tissue classification to assign the constitutive properties automatically at integration points of the computation grid. We use only very simple segmentation of the spine when determining vertebrae displacements to define loading for biomechanical models. We demonstrate the feasibility and accuracy of our approach on CT images of seven patients suffering from cancer and aortic disease. The results confirm that accurate whole-body CT image registration can be achieved using a patient-specific non-linear biomechanical model constructed without time-consuming segmentation of the whole-body images.

Wang W, Dumoulin CL, Viswanathan AN, Tse ZTH, Mehrtash A, Loew W, Norton I, Tokuda J, Seethamraju RT, Kapur T, et al. Real-time Active MR-tracking of Metallic Stylets in MR-guided Radiation Therapy. Magn Reson Med. 2015;73(5):1803-11.Abstract

PURPOSE: To develop an active MR-tracking system to guide placement of metallic devices for radiation therapy. METHODS: An actively tracked metallic stylet for brachytherapy was constructed by adding printed-circuit micro-coils to a commercial stylet. The coil design was optimized by electromagnetic simulation, and has a radio-frequency lobe pattern extending ∼5 mm beyond the strong B0 inhomogeneity region near the metal surface. An MR-tracking sequence with phase-field dithering was used to overcome residual effects of B0 and B1 inhomogeneities caused by the metal, as well as from inductive coupling to surrounding metallic stylets. The tracking system was integrated with a graphical workstation for real-time visualization. The 3 Tesla MRI catheter-insertion procedures were tested in phantoms and ex vivo animal tissue, and then performed in three patients during interstitial brachytherapy. RESULTS: The tracking system provided high-resolution (0.6 × 0.6 × 0.6 mm(3) ) and rapid (16 to 40 frames per second, with three to one phase-field dithering directions) catheter localization in phantoms, animals, and three gynecologic cancer patients. CONCLUSION: This is the first demonstration of active tracking of the shaft of metallic stylet in MR-guided brachytherapy. It holds the promise of assisting physicians to achieve better targeting and improving outcomes in interstitial brachytherapy.

Fedorov A, Penzkofer T, Hirsch MS, Flood TA, Vangel MG, Masry P, Tempany CM, Mulkern RV, Fennessy FM. The Role of Pathology Correlation Approach in Prostate Cancer Index Lesion Detection and Quantitative Analysis with Multiparametric MRI. Acad Radiol. 2015;22(5):548-55.Abstract

RATIONALE AND OBJECTIVES: Development of imaging biomarkers often relies on their correlation with histopathology. Our aim was to compare two approaches for correlating pathology to multiparametric magnetic resonance (MR) imaging (mpMRI) for localization and quantitative assessment of prostate cancer (PCa) index tumor using whole mount (WM) pathology (WMP) as the reference. MATERIALS AND METHODS: Patients (N = 30) underwent mpMRI that included diffusion-weighted imaging and dynamic contrast-enhanced (DCE) MRI at 3 T before radical prostatectomy (RP). RP specimens were processed using WM technique (WMP) and findings summarized in a standard surgical pathology report (SPR). Histology index tumor volumes (HTVs) were compared to MR tumor volumes (MRTVs) using two approaches for index lesion identification on mpMRI using annotated WMP slides as the reference (WMP) and using routine SPR as the reference. Consistency of index tumor localization, tumor volume, and mean values of the derived quantitative parameters (mean apparent diffusion coefficient [ADC], K(trans), and ve) were compared. RESULTS: Index lesions from 16 of 30 patients met the selection criteria. There was WMP/SRP agreement in index tumor in 13 of 16 patients. ADC-based MRTVs were larger (P < .05) than DCE-based MRTVs. ADC MRTVs were smaller than HTV (P < .005). There was a strong correlation between HTV and MRTV (Pearson ρ > 0.8; P < .05). No significant differences were observed in the mean values of K(trans) and ADC between the WMP and SPR. CONCLUSIONS: WMP correlation is superior to SPR for accurate localization of all index lesions. The use of WMP is however not required to distinguish significant differences of mean values of quantitative MRI parameters within tumor volume.

Aryal M, Park J, Vykhodtseva N, Zhang Y-Z, McDannold N. 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. 2015;60(6):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.

Tempany CM, Jayender J, Kapur T, Bueno R, Golby AJ, Agar NYR, Jolesz FA. Multimodal Imaging for Improved Diagnosis and Treatment of Cancers. Cancer. 2015;121(6):817-27.Abstract

The authors review methods for image-guided diagnosis and therapy that increase precision in the detection, characterization, and localization of many forms of cancer to achieve optimal target definition and complete resection or ablation. A new model of translational, clinical, image-guided therapy research is presented, and the Advanced Multimodality Image-Guided Operating (AMIGO) suite is described. AMIGO was conceived and designed to allow for the full integration of imaging in cancer diagnosis and treatment. Examples are drawn from over 500 procedures performed on brain, neck, spine, thorax (breast, lung), and pelvis (prostate and gynecologic) areas and are used to describe how they address some of the many challenges of treating brain, prostate, and lung tumors. Cancer 2015;121:817-827. © 2014 American Cancer Society.

Lu Y, Yeung C, Radmanesh A, Wiemann R, Black PM, Golby AJ. Comparative Effectiveness of Frame-Based, Frameless, and Intraoperative Magnetic Resonance Imaging–Guided Brain Biopsy Techniques. World Neurosurg. 2015;83(3):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.

Tauscher S, Tokuda J, Schreiber G, Neff T, Hata N, Ortmaier T. OpenIGTLink Interface for State Control and Visualisation of a Robot for Image-guided Therapy Systems. Int J Comput Assist Radiol Surg. 2015;10(3):285-92.Abstract

PURPOSE: The integration of a robot into an image-guided therapy system is still a time consuming process, due to the lack of a well-accepted standard for interdevice communication. The aim of this project is to simplify this procedure by developing an open interface based on three interface classes: state control, visualisation, and sensor. A state machine on the robot control is added to the concept because the robot has its own workflow during surgical procedures, which differs from the workflow of the surgeon. METHODS: A KUKA Light Weight Robot is integrated into the medical technology environment of the Institute of Mechatronic Systems as a proof of concept. Therefore, 3D Slicer was used as visualisation and state control software. For the network communication the OpenIGTLink protocol was implemented. In order to achieve high rate control of the robot the "KUKA Sunrise. Connectivity SmartServo" package was used. An exemplary state machine providing states typically used by image-guided therapy interventions, was implemented. Two interface classes, which allow for a direct use of OpenIGTLink for robot control on the one hand and visualisation on the other hand were developed. Additionally, a 3D Slicer module was written to operate the state control. RESULTS: Utilising the described software concept the state machine could be operated by the 3D Slicer module with 20 Hz cycle rate and no data loss was detected during a test phase of approximately 270s (13,640 packages). Furthermore, the current robot pose could be sent with more than 60 Hz. No influence on the performance of the state machine by the communication thread could be measured. CONCLUSION: Simplified integration was achieved by using only one programming context for the implementation of the state machine, the interfaces, and the robot control. Eventually, the exemplary state machine can be easily expanded by adding new states.