Hata N, Piper S, Jolesz FA, Tempany CM, Black PM, Morikawa S, Iseki H, Hashizume M, Kikinis R. Application of open source image guided therapy software in MR-guided therapies. Med Image Comput Comput Assist Interv. 2007;10 (Pt 1) :491-8.Abstract

We present software engineering methods to provide free open-source software for MR-guided therapy. We report that graphical representation of the surgical tools, interconnectively with the tracking device, patient-to-image registration, and MRI-based thermal mapping are crucial components of MR-guided therapy in sharing such software. Software process includes a network-based distribution mechanism by multi-platform compiling tool CMake, CVS, quality assurance software DART. We developed six procedures in four separate clinical sites using proposed software engineering and process, and found the proposed method is feasible to facilitate multicenter clinical trial of MR-guided therapies. Our future studies include use of the software in non-MR-guided therapies.

DiMaio S, Kapur T, Cleary K, Aylward S, Kazanzides P, Vosburgh KG, Ellis R, Duncan J, Farahani K, Lemke H, et al. Challenges in image-guided therapy system design. Neuroimage. 2007;37 Suppl 1 :S144-51.Abstract

System development for image-guided therapy (IGT), or image-guided interventions (IGI), continues to be an area of active interest across academic and industry groups. This is an emerging field that is growing rapidly: major academic institutions and medical device manufacturers have produced IGT technologies that are in routine clinical use, dozens of high-impact publications are published in well regarded journals each year, and several small companies have successfully commercialized sophisticated IGT systems. In meetings between IGT investigators over the last two years, a consensus has emerged that several key areas must be addressed collaboratively by the community to reach the next level of impact and efficiency in IGT research and development to improve patient care. These meetings culminated in a two-day workshop that brought together several academic and industrial leaders in the field today. The goals of the workshop were to identify gaps in the engineering infrastructure available to IGT researchers, develop the role of research funding agencies and the recently established US-based National Center for Image Guided Therapy (NCIGT), and ultimately to facilitate the transfer of technology among research centers that are sponsored by the National Institutes of Health (NIH). Workshop discussions spanned many of the current challenges in the development and deployment of new IGT systems. Key challenges were identified in a number of areas, including: validation standards; workflows, use-cases, and application requirements; component reusability; and device interface standards. This report elaborates on these key points and proposes research challenges that are to be addressed by a joint effort between academic, industry, and NIH participants.

Tang SC, Clement GT, Hynynen K. A Computer-controlled Ultrasound Pulser-receiver System for Transkull Fluid Detection using a Shear Wave Transmission Technique. IEEE Trans Ultrason Ferroelectr Freq Control. 2007;54 (9) :1772-83.Abstract

The purpose of this study was to evaluate the performance of a computer-controlled ultrasound pulser-receiver system incorporating a shear mode technique for transskull fluid detection. The presence of fluid in the sinuses of an ex vivo human skull was examined using a pulse-echo method by transmitting an ultrasound beam through the maxilla bone toward the back wall on the other side of the sinus cavity. The pulser was programmed to generate bipolar pulse trains with 5 cycles at a frequency of 1 MHz, repetition frequency of about 20 Hz, and amplitude of 100 V to drive a 1-MHz piezoelectric transducer. Shear and longitudinal waves in the maxilla bone were produced by adjusting the bone surface incident angle to 45 degrees and 0 degrees, respectively. Computer tomography (CT) scans of the skull were performed to verify the ultrasound experiment. Using the shear mode technique, the echo waveform clearly distinguishes the presence of fluid, and the estimated distance of the ultrasound traveled in the sinus is consistent with the measurement from the CT images. Contrarily, using the longitudinal mode, no detectable back wall echo was observed under the same conditions. As a conclusion, this study demonstrated that the proposed pulser-receiver system with the shear mode technique is promising for transskull fluid detecting, such as mucus in a sinus.

DiMaio SP, Samset E, Fischer G, Iordachita I, Fichtinger G, Jolesz FA, Tempany CM. Dynamic MRI scan plane control for passive tracking of instruments and devices. Med Image Comput Comput Assist Interv. 2007;10 (Pt 2) :50-8.Abstract

This paper describes a novel image-based method for tracking robotic mechanisms and interventional devices during Magnetic Resonance Image (MRI)-guided procedures. It takes advantage of the multi-planar imaging capabilities of MRI to optimally image a set of localizing fiducials for passive motion tracking in the image coordinate frame. The imaging system is servoed to adaptively position the scan plane based on automatic detection and localization of fiducial artifacts directly from the acquired image stream. This closed-loop control system has been implemented using an open-source software framework and currently operates with GE MRI scanners. Accuracy and performance were evaluated in experiments, the results of which are presented here.

Tharin S, Golby AJ. Functional brain mapping and its applications to neurosurgery. Neurosurgery. 2007;60 (4 Suppl 2) :185-201; discussion 201-2.Abstract

Functional brain mapping may be useful for both preoperative planning and intraoperative neurosurgical decision making. "Gold standard" functional studies such as direct electrical stimulation and recording are complemented by newer, less invasive techniques such as functional magnetic resonance imaging. Less invasive techniques allow more areas of the brain to be mapped in more subjects (including healthy subjects) more often (including pre- and postoperatively). Expansion of the armamentarium of tools allows convergent evidence from multiple brain mapping techniques to bear on pre- and intraoperative decision making. Functional imaging techniques are used to map motor, sensory, language, and memory areas in neurosurgical patients with conditions as diverse as brain tumors, vascular lesions, and epilepsy. In the future, coregistration of high resolution anatomic and physiological data from multiple complementary sources will be used to plan more neurosurgical procedures, including minimally invasive procedures. Along the way, new insights on fundamental processes such as the biology of tumors and brain plasticity are likely to be revealed.

Yoo S-S, Gujar N, Hu P, Jolesz FA, Walker MP. The Human Emotional Brain without Sleep - A Prefrontal Amygdala Disconnect. Curr Biol. 2007;17 (20) :R877-8.
Nguyen PL, Chen M-H, D'Amico AV, Tempany CM, Steele GS, Albert M, Cormack RA, Carr-Locke DL, Bleday R, Suh WW. Magnetic Resonance Image-guided Salvage Brachytherapy after Radiation in Select Men who Initially Presented with Favorable-risk Prostate Cancer: A Prospective Phase 2 Study. Cancer. 2007;110 (7) :1485-92.Abstract

BACKGROUND: The authors prospectively evaluated the late gastrointestinal (GI) and genitourinary (GU) toxicity and prostate-specific antigen (PSA) control of magnetic resonance imaging (MRI)-guided brachytherapy used as salvage for radiation therapy (RT) failure. METHODS: From October 2000 to October 2005, 25 men with a rising PSA level and biopsy-proven, intraprostatic cancer at least 2 years after initial RT (external beam in 13 men and brachytherapy in 12 men) who had favorable clinical features (Gleason score < or =7, PSA < 10 ng/mL, negative pelvic and bone imaging studies), received MRI-guided salvage brachytherapy to a minimum peripheral dose of 137 gray on a phase 1/2 protocol. Estimates of toxicity and cancer control were calculated using the Kaplan-Meier method. RESULTS: The median follow-up was 47 months. The 4-year estimate of grade 3 or 4 GI or GU toxicity was 30%, and 13% of patients required a colostomy and/or urostomy to repair a fistula. An interval < 4.5 years between RT courses was associated with both outcomes with a hazard ratio of 12 (95% confidence interval [95% CI], 1.4-100; P = .02) for grade 3 or 4 toxicity and 25 (95% CI, 1.1-529; P = .04) for colostomy and/or urostomy. PSA control (nadir +2 definition) was 70% at 4 years. CONCLUSIONS: The current results indicated that MRI-guided salvage brachytherapy in men who are selected based on presenting characteristics and post-failure PSA kinetics can achieve high PSA control rates, although complications requiring surgical intervention may occur in 10% to 15% of patients. Prospective randomized studies are needed to characterize the relative cancer control and toxicity after all forms of salvage local therapy.

Archip N, Clatz O, Whalen S, Kacher D, Fedorov A, Kot A, Chrisochoides N, Jolesz FA, Golby AJ, Black PM, et al. Non-rigid alignment of pre-operative MRI, fMRI, and DT-MRI with intra-operative MRI for enhanced visualization and navigation in image-guided neurosurgery. Neuroimage. 2007;35 (2) :609-24.Abstract

OBJECTIVE: The usefulness of neurosurgical navigation with current visualizations is seriously compromised by brain shift, which inevitably occurs during the course of the operation, significantly degrading the precise alignment between the pre-operative MR data and the intra-operative shape of the brain. Our objectives were (i) to evaluate the feasibility of non-rigid registration that compensates for the brain deformations within the time constraints imposed by neurosurgery, and (ii) to create augmented reality visualizations of critical structural and functional brain regions during neurosurgery using pre-operatively acquired fMRI and DT-MRI. MATERIALS AND METHODS: Eleven consecutive patients with supratentorial gliomas were included in our study. All underwent surgery at our intra-operative MR imaging-guided therapy facility and have tumors in eloquent brain areas (e.g. precentral gyrus and cortico-spinal tract). Functional MRI and DT-MRI, together with MPRAGE and T2w structural MRI were acquired at 3 T prior to surgery. SPGR and T2w images were acquired with a 0.5 T magnet during each procedure. Quantitative assessment of the alignment accuracy was carried out and compared with current state-of-the-art systems based only on rigid registration. RESULTS: Alignment between pre-operative and intra-operative datasets was successfully carried out during surgery for all patients. Overall, the mean residual displacement remaining after non-rigid registration was 1.82 mm. There is a statistically significant improvement in alignment accuracy utilizing our non-rigid registration in comparison to the currently used technology (p<0.001). CONCLUSIONS: We were able to achieve intra-operative rigid and non-rigid registration of (1) pre-operative structural MRI with intra-operative T1w MRI; (2) pre-operative fMRI with intra-operative T1w MRI, and (3) pre-operative DT-MRI with intra-operative T1w MRI. The registration algorithms as implemented were sufficiently robust and rapid to meet the hard real-time constraints of intra-operative surgical decision making. The validation experiments demonstrate that we can accurately compensate for the deformation of the brain and thus can construct an augmented reality visualization to aid the surgeon.

Archip N, Tatli S, Morrison P, Jolesz FA, Warfield SK, Silverman S. Non-rigid registration of pre-procedural MR images with intra-procedural unenhanced CT images for improved targeting of tumors during liver radiofrequency ablations. Med Image Comput Comput Assist Interv. 2007;10 (Pt 2) :969-77.Abstract

In the United States, unenhanced CT is currently the most common imaging modality used to guide percutaneous biopsy and tumor ablation. The majority of liver tumors such as hepatocellular carcinomas are visible on contrast-enhanced CT or MRI obtained prior to the procedure. Yet, these tumors may not be visible or may have poor margin conspicuity on unenhanced CT images acquired during the procedure. Non-rigid registration has been used to align images accurately, even in the presence of organ motion. However, to date, it has not been used clinically for radiofrequency ablation (RFA), since it requires significant computational infrastructure and often these methods are not sufficient robust. We have already introduced a novel finite element based method (FEM) that is demonstrated to achieve good accuracy and robustness for the problem of brain shift in neurosurgery. In this current study, we adapt it to fuse pre-procedural MRI with intra-procedural CT of liver. We also compare its performance with conventional rigid registration and two non-rigid registration methods: b-spline and demons on 13 retrospective datasets from patients that underwent RFA at our institution. FEM non-rigid registration technique was significantly better than rigid (p < 10-5), non-rigid b-spline (p < 10-4) and demons (p < 10-4) registration techniques. The results of our study indicate that this novel technology may be used to optimize placement of RF applicator during CT-guided ablations.

Sierra R, DiMaio SP, Wada J, Hata N, Székely G, Kikinis R, Jolesz FA. Patient specific simulation and navigation of ventriculoscopic interventions. Stud Health Technol Inform. 2007;125 :433-5.Abstract

In this paper a comprehensive framework for pre-operative planning, procedural skill training, and intraoperative navigation is presented. The goal of this system is to integrate surgical simulation with surgical planning in order to improve the individual treatment of patients. Various surgical approaches and new, more complex procedures can be assessed using a safe and objective platform that will allow the physicians to explore and discuss possible risks and benefits prior to the intervention. A simulation environment extends the pre-operative planning in a natural way, as it allows for direct evaluation of the surgical approach envisioned for each case. In addition, by providing intraoperative navigation based on this simulation, surgeons can carry out the previously optimized plan with higher precision and greater confidence.

Larsen S, Kikinis R, Talos I-F, Weinstein D, Wells III WM, Golby AJ. Quantitative Comparison of Functional MRI and Direct Electrocortical Stimulation for Functional Mapping. Int J Med Robot. 2007;3 (3) :262-70.Abstract

BACKGROUND: Mapping functional areas of the brain is important for planning tumour resections. With the increased use of functional magnetic resonance imaging (fMRI) for presurgical planning, there is a need to validate that fMRI activation mapping is consistent with the mapping obtained during surgery using direct electrocortical stimulation (DECS). METHODS: A quantitative comparison of DECS and fMRI mapping techniques was performed, using a patient-specific conductivity model to find the current distribution resulting from each stimulation site. The resulting DECS stimulation map was compared to the fMRI activation map, using the maximal Dice similarity coefficient (MDSC). RESULTS: Our results show some agreement between these two mapping techniques--the stimulation site with the largest MOSC was the only site that demonstrated intra-operative effect. CONCLUSIONS: There is a substantial effort to improve the techniques used to map functional areas, particularly using fMRI. It seems likely that fMRI will eventually provide a valid non-invasive means for functional mapping.

Zhang JQ, Loughlin KR, Zou KH, Haker S, Tempany CM. Role of endorectal coil magnetic resonance imaging in treatment of patients with prostate cancer and in determining radical prostatectomy surgical margin status: report of a single surgeon's practice. Urology. 2007;69 (6) :1134-7.Abstract

OBJECTIVES: To evaluate the role of the combination of endorectal coil and external multicoil array magnetic resonance imaging (MRI) in the management of prostate cancer and predicting the surgical margin status in a single-surgeon practice. METHODS: We reviewed all patients referred by a single surgeon from January 1993 to May 2002 for staging prostate MRI before selecting treatment. All MRI examinations were performed using 1.5T (Signa, GE Medical Systems) with a combination of endorectal and pelvic multicoil array. The tumor size, stage, and total gland volume on MRI, prostate-specific antigen (PSA) level, and Gleason score were all compared with the pathologic stage and diagnosis of positive surgical margins (PSMs). RESULTS: A total of 232 patients were evaluated, of whom 110 underwent radical prostatectomy, all performed by one surgeon (group 1), and 122 did not (group 2). The results showed that MRI stage, PSA level, and age were all significantly different (P <0.001). In group 1, the results showed a high specificity (99%) and accuracy (91%) for MRI staging of T3 cancer. The postoperative follow-up (median 4.5 years) revealed that 90% of men had PSA levels of less than 0.1 ng/mL. The PSM rate was 16%. No significant difference was found on MRI between the PSM group and non-PSM group. A single tumor length greater than 1.8 cm was the cutpoint above which PSMs were found (P = 0.002). CONCLUSIONS: The results of our study have shown that the combined use of clinical data and endorectal MRI can help optimize patient treatment and selection for surgery and, in a single surgeon's practice, lead to successful outcomes.

McDannold N, Barnes AS, Rybicki FJ, Oshio K, Chen N-kuei, Hynynen K, Mulkern RV. Temperature mapping considerations in the breast with line scan echo planar spectroscopic imaging. Magn Reson Med. 2007;58 (6) :1117-23.Abstract

A line-scan echo planar spectroscopic imaging (LSEPSI) sequence was used to serially acquire spectra from 4,096 voxels every 6.4 s throughout the breasts of nine female subjects in vivo. Data from the serial acquisitions were analyzed to determine the potential of the technique to characterize temperature changes using either the water frequency alone or the water-methylene frequency difference. Fluctuations of the apparent temperature change under these conditions of no heating were smallest using the water-methylene frequency difference, most probably due to a substantial reduction of motion effects both within and without the imaged plane. The approach offers considerable advantages over other methods for temperature change monitoring in the breast with magnetic resonance but suffers from some limitations, including the unavailability of lipid and water resonances in some voxels as well as a surprisingly large distribution of water-methylene frequency differences, which may preclude absolute temperature measurement.

Blumenfeld P, Hata N, DiMaio S, Zou K, Haker S, Fichtinger G, Tempany CM. Transperineal Prostate Biopsy under Magnetic Resonance Image Guidance: A Needle Placement Accuracy Study. J Magn Reson Imaging. 2007;26 (3) :688-94.Abstract

PURPOSE: To quantify needle placement accuracy of magnetic resonance image (MRI)-guided core needle biopsy of the prostate. MATERIALS AND METHODS: A total of 10 biopsies were performed with 18-gauge (G) core biopsy needle via a percutaneous transperineal approach. Needle placement error was assessed by comparing the coordinates of preplanned targets with the needle tip measured from the intraprocedural coherent gradient echo images. The source of these errors was subsequently investigated by measuring displacement caused by needle deflection and needle susceptibility artifact shift in controlled phantom studies. Needle placement error due to misalignment of the needle template guide was also evaluated. RESULTS: The mean and standard deviation (SD) of errors in targeted biopsies was 6.5 +/- 3.5 mm. Phantom experiments showed significant placement error due to needle deflection with a needle with an asymmetrically beveled tip (3.2-8.7 mm depending on tissue type) but significantly smaller error with a symmetrical bevel (0.6-1.1 mm). Needle susceptibility artifacts observed a shift of 1.6 +/- 0.4 mm from the true needle axis. Misalignment of the needle template guide contributed an error of 1.5 +/- 0.3 mm. CONCLUSION: Needle placement error was clinically significant in MRI-guided biopsy for diagnosis of prostate cancer. Needle placement error due to needle deflection was the most significant cause of error, especially for needles with an asymmetrical bevel.

Chen N-kuei, Oshio K, Panych LP. Application of k-space energy spectrum analysis to susceptibility field mapping and distortion correction in gradient-echo EPI. Neuroimage. 2006;31 (2) :609-22.Abstract
Echo-planar imaging (EPI) is widely used in functional MRI studies. It is well known that EPI quality is usually degraded by geometric distortions, when there exist susceptibility field inhomogeneities. EPI distortions may be corrected if the field maps are available. It is possible to estimate the susceptibility field gradients from the phase reconstruction of a single-TE EPI image, after a successful phase-unwrapping procedure. However, in regions affected by pronounced field gradients, the phase-unwrapping of a single-TE image may fail, and therefore the estimated field maps may be incorrect. It has been reported that the field inhomogeneity may be calculated more reliably from T2*-weighted images corresponding to multiple TEs. However, the multi-TE MRI field mapping increases the scan time. Furthermore, the measured field maps may be invalid if the subject's position changes during dynamic scans. To overcome the limitations in conventional field mapping approaches, a novel k-space energy spectrum analysis algorithm is developed, which quantifies the spatially dependent echo-shifting effect and the susceptibility field gradients directly from the k-space data of single-TE gradient-echo EPI. Using the k-space energy spectrum analysis, susceptibility field gradients can be reliably measured without phase-unwrapping, and EPI distortions can be corrected without extra field mapping scans or pulse sequence modification. The reported technique can be used to retrospectively improve the image quality of the previously acquired EPI and functional MRI data, provided that the complex-domain k-space data are still available.
Madore B, Hoge SW, Kwong R. Extension of the UNFOLD method to include free breathing. Magn Reson Med. 2006;55 (2) :352-62.Abstract
Unaliasing by Fourier-encoding the overlaps using the temporal dimension (UNFOLD) is a method to reduce the data acquisition burden in dynamic MRI. The method works by forcing aliased signals to behave in specific ways through time, so that these unwanted signals can be detected and removed. Unexpected events in time, such as displacements caused by breathing, have the potential to disturb the temporal strategy and may affect UNFOLD's ability to suppress aliasing artifacts. This work presents an extension of the UNFOLD method to accommodate temporal encoding disruptions. While the main type of disruption considered here comes from respiratory motion, other types of disruption can be envisioned, such as departures from the usual UNFOLD k-space sampling scheme. This extended version of UNFOLD was incorporated into UNFOLD-sensitivity encoding (UNFOLD-SENSE), and should also be applicable to closely related methods such as temporal SENSE (TSENSE), k-t Broaduse Linear Acquisition Speed up Technique (k-t BLAST), and k-t SENSE. Five patients were imaged with a modified version of a myocardial-perfusion sequence, and UNFOLD was used either alone or in conjunction with SENSE to obtain an acceleration of 2.0 (in three patients) or 3.0 (in two patients). In both cases this extended version of UNFOLD was able to suppress artifacts caused by the presence of breathing motion.
DiMaio SP, Kacher DF, Ellis RE, Fichtinger G, Hata N, Zientara GP, Panych LP, Kikinis R, Jolesz FA. Needle artifact localization in 3T MR images. Stud Health Technol Inform. 2006;119 :120-5.Abstract
This work explores an image-based approach for localizing needles during MRI-guided interventions, for the purpose of tracking and navigation. Susceptibility artifacts for several needles of varying thickness were imaged, in phantoms, using a 3 tesla MRI system, under a variety of conditions. The relationship between the true needle positions and the locations of artifacts within the images, determined both by manual and automatic segmentation methods, have been quantified and are presented here.
DiMaio SP, Pieper S, Chinzei K, Hata N, Balogh E, Fichtinger G, Tempany CM, Kikinis R. Robot-assisted needle placement in open-MRI: system architecture, integration and validation. Stud Health Technol Inform. 2006;119 :126-31.Abstract
This work describes an integrated system for planning and performing percutaneous procedures-such as prostate biopsy-with robotic assistance under MRI-guidance. The physician interacts with a planning interface in order to specify the set of desired needle trajectories, based on anatomical structures and lesions observed in the patient's MR images. All image-space coordinates are automatically computed, and used to position a needle guide by means of an MRI-compatible robotic manipulator, thus avoiding the limitations of the traditional fixed needle template. Direct control of real-time imaging aids visualization of the needle as it is manually inserted through the guide. Results from in-scanner phantom experiments are provided.
Kinoshita M, McDannold N, Jolesz FA, Hynynen K. Targeted delivery of antibodies through the blood-brain barrier by MRI-guided focused ultrasound. Biochem Biophys Res Commun. 2006;340 (4) :1085-90.Abstract
The blood-brain barrier (BBB) is a persistent obstacle for the local delivery of macromolecular therapeutic agents to the central nervous system (CNS). Many drugs that show potential for treating CNS diseases cannot cross the BBB and there is a need for a non-invasive targeted drug delivery method that allows local therapy of the CNS using larger molecules. We developed a non-invasive technique that allows the image-guided delivery of antibody across the BBB into the murine CNS. Here, we demonstrate that subsequent to MRI-targeted focused ultrasound induced disruption of BBB, intravenously administered dopamine D(4) receptor-targeting antibody crossed the BBB and recognized its antigens. Using MRI, we were able to monitor the extent of BBB disruption. This novel technology should be useful in delivering macromolecular therapeutic or diagnostic agents to the CNS for the treatment of various CNS disorders.
Zou KH, Bhagwat JG, Carrino JA. Statistical combination schemes of repeated diagnostic test data. Acad Radiol. 2006;13 (5) :566-72.Abstract
RATIONALE AND OBJECTIVES: When diagnostic tests are repeated and combined, a number of schemes may be adopted. Guidelines for their interpretations are required. MATERIALS AND METHODS: Three combination schemes, "and" (A), "or" (O), and "majority" (M), are considered. To evaluate these schemes, dependency by specifying kappa values quantifying repeated test agreement was structured. In a pilot study, the combined accuracies of magnetic resonance imaging using six different pulse sequences of medial collateral ligaments of the elbows of 28 cadavers, with eight having lesions artificially created surgically, were examined. Images were evaluated simultaneously by using a five-point ordinal scale. For each pulse sequence, individuals for whom the diagnosis varied from once to three repetitions were considered. RESULTS: Scheme M improves diagnostic accuracy when sensitivity and specificity of a single test exceed 0.5, with maximal improvement at 0.79. Under scheme A, sensitivity decreases to 0.38-0.59. Under scheme O, sensitivity increases to 0.53-0.79. Scheme M yields a small improvement, reaching 0.50-0.71. Under scheme A, specificity increases to 0.95-0.98. Under scheme O, specificity decreases to 0.91-0.98. Scheme M also yields a small improvement, reaching 0.94-0.98. CONCLUSION: Scheme A is recommended for ruling in diagnoses, scheme O is recommended for ruling out diagnoses, and scheme M is neutral. Consequently, different schemes may be used to optimize the target diagnostic accuracy.