Publications

2014
Schmidt EJ, Fung MM, Ciris PA, Song T, Shankaranarayanan A, Holmvang G, Gupta SN, Chaput M, Levine RA, Ruskin J, et al. Navigated DENSE Strain Imaging for Post-radiofrequency Ablation Lesion Assessment in the Swine Left Atria. Europace. 2014;16 (1) :133-41.Abstract

AIMS: Prior work has demonstrated that magnetic resonance imaging (MRI) strain can separate necrotic/stunned myocardium from healthy myocardium in the left ventricle (LV). We surmised that high-resolution MRI strain, using navigator-echo-triggered DENSE, could differentiate radiofrequency ablated tissue around the pulmonary vein (PV) from tissue that had not been damaged by radiofrequency energy, similarly to navigated 3D myocardial delayed enhancement (3D-MDE). METHODS AND RESULTS: A respiratory-navigated 2D-DENSE sequence was developed, providing strain encoding in two spatial directions with 1.2 × 1.0 × 4 mm(3) resolution. It was tested in the LV of infarcted sheep. In four swine, incomplete circumferential lesions were created around the right superior pulmonary vein (RSPV) using ablation catheters, recorded with electro-anatomic mapping, and imaged 1 h later using atrial-diastolic DENSE and 3D-MDE at the left atrium/RSPV junction. DENSE detected ablation gaps (regions with >12% strain) in similar positions to 3D-MDE (2D cross-correlation 0.89 ± 0.05). Low-strain (<8%) areas were, on average, 33% larger than equivalent MDE regions, so they include both injured and necrotic regions. Optimal DENSE orientation was perpendicular to the PV trunk, with high shear strain in adjacent viable tissue appearing as a sensitive marker of ablation lesions. CONCLUSIONS: Magnetic resonance imaging strain may be a non-contrast alternative to 3D-MDE in intra-procedural monitoring of atrial ablation lesions.

Yoshimitsu K, Kato T, Song S-E, Hata N. A Novel Four-wire-driven Robotic Catheter for Radio-frequency Ablation Treatment. Int J Comput Assist Radiol Surg. 2014;9 (5) :867-74.Abstract

PURPOSE:    Robotic catheters have been proposed to increase the efficacy and safety of the radio-frequency ablation treatment. The robotized motion of current robotic catheters mimics the motion of manual ones-namely, deflection in one direction and rotation around the catheter. With the expectation that the higher dexterity may achieve further efficacy and safety of the robotically driven treatment, we prototyped a four-wire-driven robotic catheter with the ability to deflect in two- degree-of-freedom motions in addition to rotation. METHODS:    A novel quad-directional structure with two wires was designed and developed to attain yaw and pitch motion in the robotic catheter. We performed a mechanical evaluation of the bendability and maneuverability of the robotic catheter and compared it with current manual catheters. RESULTS:    We found that the four-wire-driven robotic catheter can achieve a pitching angle of 184.7[Formula: see text] at a pulling distance of wire for 11 mm, while the yawing angle was 170.4[Formula: see text] at 11 mm. The robotic catheter could attain the simultaneous two- degree-of-freedom motions in a simulated cardiac chamber. CONCLUSION:    The results indicate that the four-wire-driven robotic catheter may offer physicians the opportunity to intuitively control a catheter and smoothly approach the focus position that they aim to ablate.

Golshan M, Sagara Y, Wexelman B, Aydogan F, Desantis S, Elise Min H, Vosburgh K, Jagadeesan J, Caragacianu D, Gombos E, et al. Pilot Study to Evaluate Feasibility of Image-Guided Breast-Conserving Therapy in the Advanced Multimodal Image-Guided Operating (AMIGO) Suite. Ann Surg Oncol. 2014;21 (10) :3356-7.Abstract

BACKGROUND: The rate of reexcision in breast-conserving surgery remains high, leading to delay in initiation of adjuvant therapy, increased cost, increased complications, and negative psychological impact to the patient.1 (-) 3 We initiated a phase 1 clinical trial to determine the feasibility of the use of intraoperative magnetic resonance imaging (MRI) to assess margins in the advanced multimodal image-guided operating (AMIGO) suite. METHODS: All patients received contrast-enhanced three-dimensional MRI while under general anesthesia in the supine position, followed by standard BCT with or without wire guidance and sentinel node biopsy. Additional margin reexcision was performed of suspicious margins and correlated to final pathology (Fig. 1). Feasibility was assessed via two components: demonstration of safety and sterility and acceptable duration of the operation and imaging; and adequacy of intraoperative MRI imaging for interpretation and its comparison to final pathology. Fig. 1 Schema of AMIGO trial RESULTS: Eight patients (mean age 48.5 years), 4 with stage I breast cancer and 4 with stage II breast cancer, were recruited. All patients underwent successful BCT in the AMIGO suite with no AMIGO-specific complications or break in sterility during surgery. The mean operative time was 113 min (range 93-146 min). CONCLUSIONS: Our experience with AMIGO suggests that it is feasible to use intraoperative MRI imaging to evaluate margin assessment in real time. Further research is required to identify modalities that will lead to a reduction in reexcision in breast cancer therapy.

Penzkofer T, Tempany CM. Prostate Cancer Detection and Diagnosis: The Role of MR and its Comparison with Other Diagnostic Modalities - A Radiologist's Perspective. NMR Biomed. 2014;27 (1) :3-15.Abstract

It is now universally recognized that many prostate cancers are over-diagnosed and over-treated. The European Randomized Study of Screening for Prostate Cancer from 2009 evidenced that, to save one man from death from prostate cancer, over 1400 men need to be screened, and 48 need to undergo treatment. The detection of prostate cancer is traditionally based on digital rectal examination (DRE) and the measurement of serum prostate-specific antigen (PSA), followed by ultrasound-guided biopsy. The primary role of imaging for the detection and diagnosis of prostate cancer has been transrectal ultrasound (TRUS) guidance during biopsy. Traditionally, MRI has been used primarily for the staging of disease in men with biopsy-proven cancer. It has a well-established role in the detection of T3 disease, planning of radiation therapy, especially three-dimensional conformal or intensity-modulated external beam radiation therapy, and planning and guiding of interstitial seed implant or brachytherapy. New advances have now established that prostate MRI can accurately characterize focal lesions within the gland, an ability that has led to new opportunities for improved cancer detection and guidance for biopsy. Two new approaches to prostate biopsy are under investigation. Both use pre-biopsy MRI to define potential targets for sampling, and the biopsy is performed either with direct real-time MR guidance (in-bore) or MR fusion/registration with TRUS images (out-of-bore). In-bore and out-of-bore MRI-guided prostate biopsies have the advantage of using the MR target definition for the accurate localization and sampling of targets or suspicious lesions. The out-of-bore method uses combined MRI/TRUS with fusion software that provides target localization and increases the sampling accuracy of TRUS-guided biopsies by integrating prostate MRI information with TRUS. Newer parameters for each imaging modality, such as sonoelastography or shear wave elastography, contrast-enhanced ultrasound and MRI elastography, show promise to further enrich datasets.

Fedorov A, Song S-E, Kapur T, Owen R, Sugar EN, Nguyen P, Wells III WM, Tempany CM. Prototype Design and Phantom Evaluation of a Device for Co-registered MRI/TRUS Imaging of the Prostate. Clin Image Based Proced. 2014;8361 :125-33.Abstract

Magnetic Resonance Imaging (MRI) and transrectal Ultrasound (TRUS) are both used in imaging interventions in men suspected of having and with prostate cancer for diagnosis as well as treatment. Due to the widespread availability and ease of use of TRUS, it is widely acknowledged that availability of spatially registered MRI/TRUS data could provide the optimal combination for characterization of prostate tissue and interventional guidance. To provide such spatially aligned data, we propose a device to support co-registered acquisition of MRI and TRUS data while maintaining a stable configuration (shape) of the prostate. We present the design and evaluation of a custom sleeve that can be introduced transrectally, and can accommodate both TRUS and endorectal MRI probes. Our experiments on a phantom have demonstrated that imaging with this sleeve did not compromise differentiation of internal structures and did not affect the quality of the MR acquisition. Reduction of the signal and contrast were however observed and quantified in the TRUS data. Further evaluation and modification of the device necessary for possible patient studies are discussed.

Gill G, Toews M, Beichel R. Robust Initialization of Active Shape Models for Lung Segmentation in CT Scans: A Feature-Based Atlas Approach. Int J Biomed Imaging. 2014;2014 :479154.Abstract

Model-based segmentation methods have the advantage of incorporating a priori shape information into the segmentation process but suffer from the drawback that the model must be initialized sufficiently close to the target. We propose a novel approach for initializing an active shape model (ASM) and apply it to 3D lung segmentation in CT scans. Our method constructs an atlas consisting of a set of representative lung features and an average lung shape. The ASM pose parameters are found by transforming the average lung shape based on an affine transform computed from matching features between the new image and representative lung features. Our evaluation on a diverse set of 190 images showed an average dice coefficient of 0.746 ± 0.068 for initialization and 0.974 ± 0.017 for subsequent segmentation, based on an independent reference standard. The mean absolute surface distance error was 0.948 ± 1.537 mm. The initialization as well as segmentation results showed a statistically significant improvement compared to four other approaches. The proposed initialization method can be generalized to other applications employing ASM-based segmentation.

Horky LL, Gerbaudo VH, Zaitsev A, Plesniak W, Hainer J, Govindarajulu U, Kikinis R, Dietrich J. Systemic Chemotherapy Decreases Brain Glucose Metabolism. Ann Clin Transl Neurol. 2014;1 (10) :788-98.Abstract

OBJECTIVE: Cancer patients may experience neurologic adverse effects, such as alterations in neurocognitive function, as a consequence of chemotherapy. The mechanisms underlying such neurotoxic syndromes remain poorly understood. We here describe the temporal and regional effects of systemically administered platinum-based chemotherapy on glucose metabolism in the brain of cancer patients. METHODS: Using sequential FDG-PET/CT imaging prior to and after administration of chemotherapy, we retrospectively characterized the effects of intravenously administered chemotherapy on brain glucose metabolism in a total of 24 brain regions in a homogenous cohort of 10 patients with newly diagnosed non-small-cell lung cancer. RESULTS: Significant alterations of glucose metabolism were found in response to chemotherapy in all gray matter structures, including cortical structures, deep nuclei, hippocampi, and cerebellum. Metabolic changes were also notable in frontotemporal white matter (WM) network systems, including the corpus callosum, subcortical, and periventricular WM tracts. INTERPRETATION: Our data demonstrate a decrease in glucose metabolism in both gray and white matter structures associated with chemotherapy. Among the affected regions are those relevant to the maintenance of brain plasticity and global neurologic function. This study potentially offers novel insights into the spatial and temporal effects of systemic chemotherapy on brain metabolism in cancer patients.

Ren H, Campos-Nanez E, Yaniv Z, Banovac F, Abeledo H, Hata N, Cleary K. Treatment Planning and Image Guidance for Radiofrequency Ablations of Large Tumors. IEEE J Biomed Health Inform. 2014;18 (3) :920-8.Abstract

This article addresses the two key challenges in computer-assisted percutaneous tumor ablation: planning multiple overlapping ablations for large tumors while avoiding critical structures, and executing the prescribed plan. Toward semiautomatic treatment planning for image-guided surgical interventions, we develop a systematic approach to the needle-based ablation placement task, ranging from preoperative planning algorithms to an intraoperative execution platform. The planning system incorporates clinical constraints on ablations and trajectories using a multiple objective optimization formulation, which consists of optimal path selection and ablation coverage optimization based on integer programming. The system implementation is presented and validated in both phantom and animal studies. The presented system can potentially be further extended for other ablation techniques such as cryotherapy.

Lee JW, Norden AD, Ligon KL, Golby AJ, Beroukhim R, Quackenbush J, Wells W, Oelschlager K, Maetzold D, Wen PY. Tumor Associated Seizures in Glioblastomas are Influenced by Survival Gene Expression in a Region-specific Manner: A Gene Expression Imaging Study. Epilepsy Res. 2014;108 (5) :843-52.Abstract

Tumor associated seizures (TAS) are common and cause significant morbidity. Both imaging and gene expression features play significant roles in determining TAS, with strong interactions between them. We describe gene expression imaging tools which allow mapping of brain regions where gene expression has significant influence on TAS, and apply these methods to study 77 patients who underwent surgical evaluation for supratentorial glioblastomas. Tumor size and location were measured from MRI scans. A 9-set gene expression profile predicting long-term survivors was obtained from RNA derived from formalin-fixed paraffin embedded tissue. A total of 32 patients (42%) experienced preoperative TAS. Tumor volume was smaller (31.1 vs. 58.8 cubic cm, p<0.001) and there was a trend toward median survival being higher (48.4 vs. 32.7 months, p=0.055) in patients with TAS. Although the expression of only OLIG2 was significantly lower in patients with TAS in a groupwise analysis, gene expression imaging analysis revealed regions with significantly lower expression of OLIG2 and RTN1 in patients with TAS. Gene expression imaging is a powerful technique that demonstrates that the influence of gene expression on TAS is highly region specific. Regional variability should be evaluated with any genomic or molecular markers of solid brain lesions.

Aryal M, Arvanitis CD, Alexander PM, McDannold N. Ultrasound-Mediated Blood-brain Barrier Disruption for Targeted Drug Delivery in the Central Nervous System. Adv Drug Deliv Rev. 2014;72 :94-109.Abstract

The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB.

Schmidt EJ, Tse ZTH, Reichlin TR, Michaud GF, Watkins RD, Butts-Pauly K, Kwong RY, Stevenson W, Schweitzer J, Byrd I, et al. Voltage-based Device Tracking in a 1.5 Tesla MRI during Imaging: Initial Validation in Swine Models. Magn Reson Med. 2014;71 (3) :1197-209.Abstract

PURPOSE: Voltage-based device-tracking (VDT) systems are commonly used for tracking invasive devices in electrophysiological cardiac-arrhythmia therapy. During electrophysiological procedures, electro-anatomic mapping workstations provide guidance by integrating VDT location and intracardiac electrocardiogram information with X-ray, computerized tomography, ultrasound, and MR images. MR assists navigation, mapping, and radiofrequency ablation. Multimodality interventions require multiple patient transfers between an MRI and the X-ray/ultrasound electrophysiological suite, increasing the likelihood of patient-motion and image misregistration. An MRI-compatible VDT system may increase efficiency, as there is currently no single method to track devices both inside and outside the MRI scanner. METHODS: An MRI-compatible VDT system was constructed by modifying a commercial system. Hardware was added to reduce MRI gradient-ramp and radiofrequency unblanking pulse interference. VDT patches and cables were modified to reduce heating. Five swine cardiac VDT electro-anatomic mapping interventions were performed, navigating inside and thereafter outside the MRI. RESULTS: Three-catheter VDT interventions were performed at >12 frames per second both inside and outside the MRI scanner with <3 mm error. Catheters were followed on VDT- and MRI-derived maps. Simultaneous VDT and imaging was possible in repetition time >32 ms sequences with <0.5 mm errors, and <5% MRI signal-to-noise ratio (SNR) loss. At shorter repetition times, only intracardiac electrocardiogram was reliable. Radiofrequency heating was <1.5°C. CONCLUSION: An MRI-compatible VDT system is feasible.

2013
Pernelle G, Kapur T, Mehrtash A, Penzkofer T, Damato A, Barber L, Schmidt E, Viswanathan A, Cormack RA. Automated Interstitial Brachytherapy Catheter Localization From Volumetric MR Data. Med Phys. 2013;40 (6Part2) :94.Abstract

PURPOSE: This work seeks to validate an automatic method for extracting interstitial catheter locations from volumetric MR data. METHODS: A 3D b-SSFP (balanced Steady State Free Precession) MRI sequence was used to enhance catheter detection, utilizing a controlled enlargement of size caused by magnetic susceptibility artifacts . Starting with a user-provided needle-tip location, the needle extraction algorithm searched the MR image for segments that maximized the "needle likelihood" and iteratively fit Bezier curves to these segments. To validate the geometry of extracted catheters, a phantom was constructed from transparent gel wax. An obturator was placed at the center of a transparent plastic container, and wax gel was melted and poured around it. A Syed-Neblett template was then placed at one end of the obturator and 12 MR compatible catheters were inserted into the gel. The catheter trajectories extracted from the MR scan by the algorithm were compared to a CT scan. The algorithm was applied to patient scans under an IRB approved protocol. RESULTS: The volumetric b-SSFP sequence produced an artifact enhancement that enabled brachytherapy catheters to be distinguished from other signal voids. Comparison in a phantom of catheter locations extracted automatically from MR to those extracted manually from CT showed agreement of 3.5 mm Hausdorff Distance. When applied to patient scans, the presence of low signal regions between template and the target tumor required some manual intervention to ensure proper catheter extraction. CONCLUSION: An automatic algorithm for extracting interstitial catheter locations from MR scans has been developed. Using a b-SSFP sequence allowed an iterative curve fitting algorithm to track MR artifacts from user provided tips to template. This algorithm should prove helpful to facilitate MR based treatment planning for interstitial brachytherapy. NIH P41 EB015898.

Wang W, Gao Y, Mehrtash A, Seethmaraju R, Kapur T, Vishwanathan A, Schmidt E, Cormack RA. Real-Time Catheter Tracking and Visualization in MR-Guided Brachytherapy. Med Phys. 2013;40 (6Part30) :505.Abstract

PURPOSE: The challenge of catheter-tip visualization for interstitial needle placement in gynecologic brachytherapy remains unmet. We evaluate an approach to actively track tip locations and visualize catheter trajectories and surrounding soft-tissue in real-time during an intervention. The methods include development of clinical needles with magnetic resonance (MR) tracked microcoils, an MR tracking and rapid imaging sequence and integration with a graphical workstation for visualization. METHODS: An active tracking device was built based on a commercial catheter which consists of a hollow tube and a central needle with microcoils at the distal end. An MR tracking sequence was developed (isotropic resolution: 0.6 mm, frame rate: 40 updates/sec). It runs continuously during navigation or interleaves with real-time imaging (3 frames/sec), where image position/orientation are automatically set to provide visualization of anatomy around the catheter. The catheter-tip position/orientation was passed to the workstation for visualization. Needle shapes were superimposed on pre-acquired high-resolution images or on the intra-procedural images. RESULTS: MR-guided catheter placement procedures were conducted in a gel phantom and an animal model. High-resolution 3D MR scans were acquired and loaded into the workstation for navigation. During insertion, the catheter tips were visualized advancing on a 3D anatomic model and on assigned planes. Real-time imaging with slice continuously updating at the instantaneous tip positions was also performed. Both methods served well to guide catheter placement. After insertion, complete catheter trajectories were rendered by recording tip positions as needles were pulled out and overlaid on the images, to support treatment planning. CONCLUSION: We demonstrated the feasibility of active catheter tracking and visualization in MR-guided brachytherapy. This will facilitate accurate and time-efficient catheter insertion by providing on-line identification of catheter position, and visualization of anatomy ahead of the catheter tip. This enables identifying preferential paths to target locations, and reduces the risk to critical organs. FUNDING SOURCES: NIH P41 EB015898; AHA 10SDG261039.

Cormack RA, Federov A, Fennesy F, Penzkofer T, Tuncali K, Tempany CM, Nguyen P. Constraints On Focal Brachytherapy Treatments for Early Stage Prostate Cancer: A Comparison of Isotopes. Med Phys. 2013;40 (6Part3) :104.Abstract

PURPOSE: Patients with favorable-risk prostate cancer may be attracted to focal therapy aimed at the dominant intraprostatic lesion as a middle ground between the morbidity of full gland treatment and the uncertainty of observation. The various approaches involve isotopes having different energies implying different dosimetric characteristics. This work seeks to determine if choice of isotope makes a substantial difference in the fraction of prostate that may be implanted as a function of implant volume and rectal dose limit. METHODS: Representations of prostate, urethra and rectum were generated from MR scans as part of an IRB approved medical record review of patients with confirmed low risk prostate cancer. Anatomic structures were digitized on a 2.5 × 2.5 × 5.0 mm grid. Focal implants were simulated by placement of a single source. All prostate points 5 mm or further from a sensitive structure were considered as potential implant location. Dose distributions were calculated for implants of 125I, 109Pd and 192Ir. The fraction of potential implant locations that respected normal tissue constraints (rectum: 10-100% of Rx, urethra 100-200% of Rx) as a function of prescription radius was recorded. RESULTS: The fraction of the prostate implantable for a given prescription radius primarily depends on the normal tissue dose limits that are to be respected with a secondary dependence on isotope. Prescription radius less than 1 cm and rectal dose constraints greater than 50% of prescription dose allow a substantial portion of the gland to be considered for a focal implant. Detailed results are presented as a function of normal tissue constraints and prescription radius. CONCLUSION: While isotope choice does affect the implantable volume, the effect is secondary to the choice of prescription parameters. Choice of focal brachytherapy approach may be made based on consideration of duration of irradiation or clinical concerns. NIH P41 EB015898.

Wright J. Surgery: The Eyes of the Operation. Nature. 2013;502 (7473) :S88-9.Abstract

Real-time imaging of a patient's body is guiding surgeons and radiologists past healthy tissue to the diseased cells.

 

In the early 1990s, Jolesz pioneered the use of MRI in operations, taking scans during brain surgery for the first time. When this was successful, it became clear that the best way to guide treatment would be to combine as many forms of imaging as possible, says Jolesz. In September 2011, a grant from the US National Institutes of Health led to the Advanced Multimodality Image Guided Operating (AMIGO) suite — a three-room operating suite that includes an MRI scanner, a CT and positron emission tomography (PET) scanner, and an advanced three-dimensional ultrasound and navigation system.

Researchers are exploring how to combine the resources at AMIGO to refine treatments. Imaging during surgery can address the problem of overtreating early-stage tumours, such as those found during routine lung CT scans on smokers. Small lumps are difficult to locate so surgeons may end up removing large pieces of lung tissue that will never grow back, says Raphael Bueno, a thoracic surgeon at Brigham and Women's Hospital. As part of an ongoing clinical trial, Bueno has devised a method to use a CT scan to guide the placement of a small hook-like device in the lesion. The hook is attached to surgical thread that reaches out of the lung. During surgery the thread acts as a guide, allowing Bueno to snip out only the affected tissue.

 

 

Kapur T, Tempany CM, Jolesz FA. Proceedings of the 6th Image Guided Therapy Workshop. 2013;6 :1-87. 2013 IGT Workshop Proceedings
Shriver S, Knierim KE, O'Shea JP, Glover GH, Golby AJ. Pneumatically driven finger movement: a novel passive functional MR imaging technique for presurgical motor and sensory mapping. AJNR Am J Neuroradiol. 2013;34 (1) :E5-7.Abstract
Two of the most common reasons for failure to obtain adequate preoperative functional data are inadequate task performance and excessive head motion. With an MR imaging-compatible pneumatically driven manipulandum, passive motor tasks elicited reproducible contralateral activation in the M1 and S1 in 10 healthy controls and 6 patients. The SMA was localized in all healthy controls and in 5 of 6 patients. Head motion was reduced in passive tasks compared with active tasks.
Kolesov I, Lee J, Vela P, Tannenbaum A. Stochastic Image Registration with User Constraints. Proc SPIE Int Soc Opt Eng. 2013;8669.Abstract
Constrained registration is an active area of research and is the focus of this work. This note describes a non-rigid image registration framework for incorporating landmark constraints. Points that must remain stationary are selected, the user chooses the spatial extent of the inputs, and an automatic step computes the deformable registration, respecting the constraints. Parametrization of the deformation field is by an additive composition of a similarity transformation and a set of Gaussian radial basis functions. The bases' centers, variances, and weights are determined with a global optimization approach that is introduced. This approach is based on the particle filter for performing constrained optimization; it explores a series of states defining a deformation field that is physically meaningful (i.e., invertible) and prevents chosen points from moving. Results on synthetic two dimensional images are presented.
Seifabadi R, Cho NBJ, Song S-E, Tokuda J, Hata N, Tempany CM, Fichtinger G, Iordachita I. Accuracy Study of a Robotic System for MRI-guided Prostate Needle Placement. Int J Med Robot. 2013;9 (3) :305-16.Abstract

BACKGROUND: Accurate needle placement is the first concern in percutaneous MRI-guided prostate interventions. In this phantom study, different sources contributing to the overall needle placement error of a MRI-guided robot for prostate biopsy have been identified, quantified and minimized to the possible extent. METHODS: The overall needle placement error of the system was evaluated in a prostate phantom. This error was broken into two parts: the error associated with the robotic system (called 'before-insertion error') and the error associated with needle-tissue interaction (called 'due-to-insertion error'). Before-insertion error was measured directly in a soft phantom and different sources contributing into this part were identified and quantified. A calibration methodology was developed to minimize the 4-DOF manipulator's error. The due-to-insertion error was indirectly approximated by comparing the overall error and the before-insertion error. The effect of sterilization on the manipulator's accuracy and repeatability was also studied. RESULTS: The average overall system error in the phantom study was 2.5 mm (STD = 1.1 mm). The average robotic system error in the Super Soft plastic phantom was 1.3 mm (STD = 0.7 mm). Assuming orthogonal error components, the needle-tissue interaction error was found to be approximately 2.13 mm, thus making a larger contribution to the overall error. The average susceptibility artifact shift was 0.2 mm. The manipulator's targeting accuracy was 0.71 mm (STD = 0.21 mm) after robot calibration. The robot's repeatability was 0.13 mm. Sterilization had no noticeable influence on the robot's accuracy and repeatability. CONCLUSIONS: The experimental methodology presented in this paper may help researchers to identify, quantify and minimize different sources contributing into the overall needle placement error of an MRI-guided robotic system for prostate needle placement. In the robotic system analysed here, the overall error of the studied system remained within the acceptable range.

Eberlin LS, Norton I, Orringer D, Dunn IF, Liu X, Ide JL, Jarmusch AK, Ligon KL, Jolesz FA, Golby AJ, et al. Ambient Mass Spectrometry for the Intraoperative Molecular Diagnosis of Human Brain Tumors. Proc Natl Acad Sci U S A. 2013;110 (5) :1611-6.Abstract

The main goal of brain tumor surgery is to maximize tumor resection while preserving brain function. However, existing imaging and surgical techniques do not offer the molecular information needed to delineate tumor boundaries. We have developed a system to rapidly analyze and classify brain tumors based on lipid information acquired by desorption electrospray ionization mass spectrometry (DESI-MS). In this study, a classifier was built to discriminate gliomas and meningiomas based on 36 glioma and 19 meningioma samples. The classifier was tested and results were validated for intraoperative use by analyzing and diagnosing tissue sections from 32 surgical specimens obtained from five research subjects who underwent brain tumor resection. The samples analyzed included oligodendroglioma, astrocytoma, and meningioma tumors of different histological grades and tumor cell concentrations. The molecular diagnosis derived from mass-spectrometry imaging corresponded to histopathology diagnosis with very few exceptions. Our work demonstrates that DESI-MS technology has the potential to identify the histology type of brain tumors. It provides information on glioma grade and, most importantly, may help define tumor margins by measuring the tumor cell concentration in a specimen. Results for stereotactically registered samples were correlated to preoperative MRI through neuronavigation, and visualized over segmented 3D MRI tumor volume reconstruction. Our findings demonstrate the potential of ambient mass spectrometry to guide brain tumor surgery by providing rapid diagnosis, and tumor margin assessment in near-real time.

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