Publications

2015
Calligaris D, Feldman DR, Norton I, Brastianos PK, Dunn IF, Santagata S, Agar NYR. Molecular Typing of Meningiomas by Desorption Electrospray Ionization Mass Spectrometry Imaging for Surgical Decision-Making. Int J Mass Spectrom. 2015;377 :690-8.Abstract

Meningiomas are the most frequent intracranial tumors. The majority is benign slow-growing tumors but they can be difficult to treat depending on their location and size. While meningiomas are well delineated on magnetic resonance imaging by their uptake of contrast, surgical limitations still present themselves from not knowing the extent of invasion of the dura matter by meningioma cells. The development of tools to characterize tumor tissue in real or near real time could prevent recurrence after tumor resection by allowing for more precise surgery, i.e. removal of tumor with preservation of healthy tissue. The development of ambient ionization mass spectrometry for molecular characterization of tissue and its implementation in the surgical decision-making workflow carry the potential to fulfill this need. Here, we present the characterization of meningioma and dura mater by desorption electrospray ionization mass spectrometry to validate the technique for the molecular assessment of surgical margins and diagnosis of meningioma from surgical tissue in real-time. Nine stereotactically resected surgical samples and three autopsy samples were analyzed by standard histopathology and mass spectrometry imaging. All samples indicated a strong correlation between results from both techniques. We then highlight the value of desorption electrospray ionization mass spectrometry for the molecular subtyping/subgrouping of meningiomas from a series of forty genetically characterized specimens. The minimal sample preparation required for desorption electrospray ionization mass spectrometry offers a distinct advantage for applications relying on real-time information such as surgical decision-making. The technology here was tested to distinguish meningioma from dura mater as an approach to precisely define surgical margins. In addition we classify meningiomas into fibroblastic and meningothelial subtypes and more notably recognize meningiomas with NF2 genetic aberrations.

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.

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. 

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.

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.

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.

Fedorov A, Khallaghi S, Sánchez AC, Lasso A, Fels S, Tuncali K, Sugar EN, Kapur T, Zhang C, Wells III WM, et al. Open-source Image Registration for MRI-TRUS Fusion-guided Prostate Interventions. Int J Comput Assist Radiol Surg. 2015;10 (6) :925-34.Abstract

PURPOSE: We propose two software tools for non-rigid registration of MRI and transrectal ultrasound (TRUS) images of the prostate. Our ultimate goal is to develop an open-source solution to support MRI-TRUS fusion image guidance of prostate interventions, such as targeted biopsy for prostate cancer detection and focal therapy. It is widely hypothesized that image registration is an essential component in such systems. METHODS: The two non-rigid registration methods are: (1) a deformable registration of the prostate segmentation distance maps with B-spline regularization and (2) a finite element-based deformable registration of the segmentation surfaces in the presence of partial data. We evaluate the methods retrospectively using clinical patient image data collected during standard clinical procedures. Computation time and Target Registration Error (TRE) calculated at the expert-identified anatomical landmarks were used as quantitative measures for the evaluation. RESULTS: The presented image registration tools were capable of completing deformable registration computation within 5 min. Average TRE was approximately 3 mm for both methods, which is comparable with the slice thickness in our MRI data. Both tools are available under nonrestrictive open-source license. CONCLUSIONS: We release open-source tools that may be used for registration during MRI-TRUS-guided prostate interventions. Our tools implement novel registration approaches and produce acceptable registration results. We believe these tools will lower the barriers in development and deployment of interventional research solutions and facilitate comparison with similar tools.

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.

Yamauchi FI, Penzkofer T, Fedorov A, Fennessy FM, Chu R, Maier SE, Tempany CM, Mulkern RV, Panych LP. Prostate Cancer Discrimination in the Peripheral Zone with a Reduced Field-of-view T2-mapping MRI Sequence. Magn Reson Imaging. 2015;33 (5) :525-30.Abstract

OBJECTIVES: To evaluate the performance of T2 mapping in discriminating prostate cancer from normal prostate tissue in the peripheral zone using a practical reduced field-of-view MRI sequence requiring less than 3 minutes of scan time. MATERIALS AND METHODS: Thirty-six patients with biopsy-proven peripheral zone prostate cancer without prior treatment underwent routine multiparametric MRI at 3.0T with an endorectal coil. An Inner-Volume Carr-Purcell-Meiboom-Gill imaging sequence that required 2.8 minutes to obtain data for quantitative T2 mapping covering the entire prostate gland was added to the routine multiparametric protocol. Suspected cancer (SC) and suspected healthy (SH) tissue in the peripheral zone were identified in consensus by three radiologists and were correlated with available biopsy results. Differences in mean T2 values in SC and SH regions-of-interest (ROIs) were tested for significance using unpaired Student's two-tailed t-test. The area under the receiver operating characteristic curve was used to assess the optimal threshold T2 value for cancer discrimination. RESULTS: ROI analyses revealed significantly (p<0.0001) shorter T2 values in SC (85.4±12.3ms) compared to SH (169.6±38.7ms). An estimated T2 threshold of 99ms yielded a sensitivity of 92% and a specificity of 97% for prostate cancer discrimination. CONCLUSIONS: Quantitative values derived from this clinically practical T2-mapping sequence allow high precision discrimination between healthy and cancerous peripheral zone in the prostate.

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.
Poynton CB, Jenkinson M, Adalsteinsson E, Sullivan EV, Pfefferbaum A, Wells III WM. Quantitative Susceptibility Mapping by Inversion of a Perturbation Field Model: Correlation with Brain Iron in Normal Aging. IEEE Trans Med Imaging. 2015;34 (1) :339-53.Abstract

There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson's, Huntington's, and Alzheimer's disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or "QSIP." The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B0 inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase, and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in vivo FDRI: statistically significant Spearman correlations ranging from Rho=0.905 to Rho=1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions.

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.

Chen Z, Tie Y, Olubiyi O, Rigolo L, Mehrtash A, Norton I, Pasternak O, Rathi Y, Golby AJ, O'Donnell LJ. Reconstruction of the Arcuate Fasciculus for Surgical Planning in the Setting of Peritumoral Edema using Two-tensor Unscented Kalman Filter Tractography. Neuroimage Clin. 2015;7 :815-22.Abstract

BACKGROUND: Diffusion imaging tractography is increasingly used to trace critical fiber tracts in brain tumor patients to reduce the risk of post-operative neurological deficit. However, the effects of peritumoral edema pose a challenge to conventional tractography using the standard diffusion tensor model. The aim of this study was to present a novel technique using a two-tensor unscented Kalman filter (UKF) algorithm to track the arcuate fasciculus (AF) in brain tumor patients with peritumoral edema. METHODS: Ten right-handed patients with left-sided brain tumors in the vicinity of language-related cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-Tesla magnetic resonance imaging (MRI) including a diffusion-weighted dataset with 31 directions. Fiber tractography was performed using both single-tensor streamline and two-tensor UKF tractography. A two-regions-of-interest approach was applied to perform the delineation of the AF. Results from the two different tractography algorithms were compared visually and quantitatively. RESULTS: Using single-tensor streamline tractography, the AF appeared disrupted in four patients and contained few fibers in the remaining six patients. Two-tensor UKF tractography delineated an AF that traversed edematous brain areas in all patients. The volume of the AF was significantly larger on two-tensor UKF than on single-tensor streamline tractography (p < 0.01). CONCLUSIONS: Two-tensor UKF tractography provides the ability to trace a larger volume AF than single-tensor streamline tractography in the setting of peritumoral edema in brain tumor patients.

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.

Patil VD, Gupta R, San José Estépar R, Lacson R, Cheung A, Wong JM, Popp JA, Golby AJ, Ogilvy C, Vosburgh KG. Smart Stylet: The Development and Use of a Bedside External Ventricular Drain Image-Guidance System. Stereotact Funct Neurosurg. 2015;93 (1) :50-8.Abstract

BACKGROUND: Placement accuracy of ventriculostomy catheters is reported in a wide and variable range. Development of an efficient image-guidance system may improve physician performance and patient safety. OBJECTIVE: We evaluate the prototype of Smart Stylet, a new electromagnetic image-guidance system for use during bedside ventriculostomy. METHODS: Accuracy of the Smart Stylet system was assessed. System operators were evaluated for their ability to successfully target the ipsilateral frontal horn in a phantom model. RESULTS: Target registration error across 15 intracranial targets ranged from 1.3 to 4.6 mm (mean 3.1 mm). Using Smart Stylet guidance, a test operator successfully passed a ventriculostomy catheter to a shifted ipsilateral frontal horn 20/20 (100%) times from the frontal approach in a skull phantom. Without Smart Stylet guidance, the operator was successful 4/10 (40%) times from the right frontal approach and 6/10 (60%) times from the left frontal approach. In a separate experiment, resident operators were successful 2/4 (50%) times when targeting the shifted ipsilateral frontal horn with Smart Stylet guidance and 0/4 (0%) times without image guidance using a skull phantom. CONCLUSIONS: Smart Stylet may improve the ability to successfully target the ventricles during frontal ventriculostomy.

Arvanitis CD, Clement GT, McDannold N. Transcranial Assessment and Visualization of Acoustic Cavitation: Modeling and Experimental Validation. IEEE Trans Med Imaging. 2015;34 (6) :1270-81.Abstract
The interaction of ultrasonically-controlled microbubble oscillations with tissues and biological media has been shown to induce a wide range of bioeffects that may have significant impact on therapy and diagnosis of brain diseases and disorders. However, the inherently non-linear microbubble oscillations combined with the micrometer and microsecond scales involved in these interactions and the limited methods to assess and visualize them transcranially hinder both their optimal use and translation to the clinics. To overcome these challenges, we present a framework that combines numerical simulations with multimodality imaging to assess and visualize the microbubble oscillations transcranially. In the present work, microbubble oscillations were studied with an integrated US and MR imaging guided clinical FUS system. A high-resolution brain CT scan was also co-registered to the US and MR images and the derived acoustic properties were used as inputs to two- and three-dimensional Finite Difference Time Domain simulations that matched the experimental conditions and geometry. Synthetic point sources by either a Gaussian function or the output of a microbubble dynamics model were numerically excited and propagated through the skull towards a virtual US imaging array. Using passive acoustic mapping (PAM) that was refined to incorporate variable speed of sound, we were able to correct the aberrations introduced by the skull and substantially improve the PAM resolution. The good agreement between the simulations incorporating microbubble emissions and experimentally-determined PAMs suggest that this integrated approach can provide a clinically-relevant framework and more control over this nonlinear and dynamic process.
Penzkofer T, Tuncali K, Fedorov A, Song S-E, Tokuda J, Fennessy FM, Vangel MG, Kibel AS, Mulkern RV, Wells WM, et al. Transperineal In-Bore 3-T MR Imaging-guided Prostate Biopsy: A Prospective Clinical Observational Study. Radiology. 2015;274 (1) :170-80.Abstract

PURPOSE: To determine the detection rate, clinical relevance, Gleason grade, and location of prostate cancer ( PCa prostate cancer ) diagnosed with and the safety of an in-bore transperineal 3-T magnetic resonance (MR) imaging-guided prostate biopsy in a clinically heterogeneous patient population. MATERIALS AND METHODS: This prospective retrospectively analyzed study was HIPAA compliant and institutional review board approved, and informed consent was obtained. Eighty-seven men (mean age, 66.2 years ± 6.9) underwent multiparametric endorectal prostate MR imaging at 3 T and transperineal MR imaging-guided biopsy. Three subgroups of patients with at least one lesion suspicious for cancer were included: men with no prior PCa prostate cancer diagnosis, men with PCa prostate cancer who were undergoing active surveillance, and men with treated PCa prostate cancer and suspected recurrence. Exclusion criteria were prior prostatectomy and/or contraindication to 3-T MR imaging. The transperineal MR imaging-guided biopsy was performed in a 70-cm wide-bore 3-T device. Overall patient biopsy outcomes, cancer detection rates, Gleason grade, and location for each subgroup were evaluated and statistically compared by using χ(2) and one-way analysis of variance followed by Tukey honestly significant difference post hoc comparisons. RESULTS: Ninety biopsy procedures were performed with no serious adverse events, with a mean of 3.7 targets sampled per gland. Cancer was detected in 51 (56.7%) men: 48.1% (25 of 52) with no prior PCa prostate cancer , 61.5% (eight of 13) under active surveillance, and 72.0% (18 of 25) in whom recurrence was suspected. Gleason pattern 4 or higher was diagnosed in 78.1% (25 of 32) in the no prior PCa prostate cancer and active surveillance groups. Gleason scores were not assigned in the suspected recurrence group. MR targets located in the anterior prostate had the highest cancer yield (40 of 64, 62.5%) compared with those for the other parts of the prostate (P < .001). CONCLUSION: In-bore 3-T transperineal MR imaging-guided biopsy, with a mean of 3.7 targets per gland, allowed detection of many clinically relevant cancers, many of which were located anteriorly.

2014
Kapur T, Tempany CM, Jolesz FA. Proceedings of the 7th Image Guided Therapy Workshop. Image Guided Therapy Workshop. 2014;7 :1-60. 2014 IGT Workshop Proceedings
Phillips JG, Aizer AA, Chen M-H, Zhang D, Hirsch MS, Richie JP, Tempany CM, Williams S, Hegde JV, Loffredo MJ, et al. The Effect of Differing Gleason Scores at Biopsy on the Odds of Upgrading and the Risk of Death from Prostate Cancer. Clin Genitourin Cancer. 2014;12 (5) :e181-7.Abstract

INTRODUCTION/BACKGROUND: The GS is an established prostate cancer prognostic factor. Whether the presence of differing GSs at biopsy (eg, 4+3 and 3+3), which we term ComboGS, improves the prognosis that would be predicted based on the highest GS (eg, 4+3) because of decreased upgrading is unknown. Therefore, we evaluated the odds of upgrading at time of radical prostatectomy (RP) and the risk of PCSM when ComboGS was present versus absent. PATIENTS AND METHODS: Logistic and competing risks regression were performed to assess the effect that ComboGS had on the odds of upgrading at time of RP in the index (n = 134) and validation cohorts (n = 356) and the risk of PCSM after definitive therapy in a long-term cohort (n = 666), adjusting for known predictors of these end points. We calculated and compared the area under the curve using a receiver operating characteristic analysis when ComboGS was included versus excluded from the upgrading models. RESULTS: ComboGS was associated with decreased odds of upgrading (index: adjusted odds ratio [AOR], 0.14; 95% confidence interval [CI], 0.04-0.50; P = .003; validation: AOR, 0.24; 95% CI, 0.11-0.51; P < .001) and added significantly to the predictive value of upgrading for the in-sample index (P = .02), validation (P = .003), and out-of-sample prediction models (P = .002). ComboGS was also associated with a decreased risk of PCSM (adjusted hazard ratio, 0.40; 95% CI, 0.19-0.85; P = .02). CONCLUSION: Differing biopsy GSs are associated with a lower odds of upgrading and risk of PCSM. If validated, future randomized noninferiority studies evaluating deescalated treatment approaches in men with ComboGS could be considered.

Mehrtash A, Damato A, Pernelle G, Barber L, Farhat N, Viswanathan A, Cormack R, Kapur T. EM-Navigated Catheter Placement for Gynecologic Brachytherapy: An Accuracy Study. Proc SPIE Int Soc Opt Eng. 2014;9036 :90361F.Abstract
Gynecologic malignancies, including cervical, endometrial, ovarian, vaginal and vulvar cancers, cause significant mortality in women worldwide. The standard care for many primary and recurrent gynecologic cancers consists of chemoradiation followed by brachytherapy. In high dose rate (HDR) brachytherapy, intracavitary applicators and/or interstitial needles are placed directly inside the cancerous tissue so as to provide catheters to deliver high doses of radiation. Although technology for the navigation of catheters and needles is well developed for procedures such as prostate biopsy, brain biopsy, and cardiac ablation, it is notably lacking for gynecologic HDR brachytherapy. Using a benchtop study that closely mimics the clinical interstitial gynecologic brachytherapy procedure, we developed a method for evaluating the accuracy of image-guided catheter placement. Future bedside translation of this technology offers the potential benefit of maximizing tumor coverage during catheter placement while avoiding damage to the adjacent organs, for example bladder, rectum and bowel. In the study, two independent experiments were performed on a phantom model to evaluate the targeting accuracy of an electromagnetic (EM) tracking system. The procedure was carried out using a laptop computer (2.1GHz Intel Core i7 computer, 8GB RAM, Windows 7 64-bit), an EM Aurora tracking system with a 1.3mm diameter 6 DOF sensor, and 6F (2 mm) brachytherapy catheters inserted through a Syed-Neblett applicator. The 3D Slicer and PLUS open source software were used to develop the system. The mean of the targeting error was less than 2.9mm, which is comparable to the targeting errors in commercial clinical navigation systems.

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