Publications

2015
Pasternak O, Westin C-F, Dahlben B, Bouix S, Kubicki M. The Extent of Diffusion MRI Markers of Neuroinflammation and White Matter Deterioration in Chronic Schizophrenia. Schizophr Res. 2015;161 (1) :113-8.Abstract

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

Gill RR, Zheng Y, Barlow JS, Jayender J, Girard EE, Hartigan PM, Chirieac LR, Belle-King CJ, Murray K, Sears C, et al. Image-guided Video Assisted Thoracoscopic Surgery (iVATS) - Phase I-II Clinical Trial. J Surg Oncol. 2015;112 (1) :18-25.Abstract

PURPOSE: To facilitate localization and resection of small lung nodules, we developed a prospective clinical trial (ClinicalTrials.gov number NCT01847209) for a novel surgical approach which combines placement of fiducials using intra-operative C-arm computed tomography (CT) guidance with standard thoracoscopic resection technique using image-guided video-assisted thoracoscopic surgery (iVATS). METHODS: Pretrial training was performed in a porcine model using C-arm CT and needle guidance software. Methodology and workflow for iVATS was developed, and a multi-modality team was trained. A prospective phase I-II clinical trial was initiated with the goal of recruiting eligible patients with small peripheral pulmonary nodules. Intra-operative C-arm CT scan was utilized for guidance of percutaneous marking with two T-bars (Kimberly-Clark, Roswell, GA) followed by VATS resection of the tumor. RESULTS: Twenty-five patients were enrolled; 23 underwent iVATS, one withdrew, and one lesion resolved. Size of lesions were: 0.6-1.8 cm, mean = 1.3 ± 0.38 cm.. All 23 patients underwent complete resection of their lesions. CT imaging of the resected specimens confirmed the removal of the T-bars and the nodule. Average and total procedure radiation dose was in the acceptable low range (median = 1501 μGy*m(2), range 665-16,326). There were no deaths, and all patients were discharged from the hospital (median length of stay = 4 days, range 2-12). Three patients had postoperative complications: one prolonged air-leak, one pneumonia, and one ileus. CONCLUSIONS: A successful and safe step-wise process has been established for iVATS, combining intra-operative C-arm CT scanning and thoracoscopic surgery in a hybrid operating room.

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

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

Olubiyi O, Ozdemir A, Incekara F, Tie Y, Dolati P, Hsu L, Santagata S, Chen Z, Rigolo L, Golby AJ. Intraoperative Magnetic Resonance Imaging in Intracranial Glioma Resection: A Single-Center, Retrospective Blinded Volumetric Study. World Neurosurg. 2015;84 (2) :528-36.Abstract

BACKGROUND: Intraoperative magnetic resonance imaging (IoMRI) was devised to overcome brain shifts during craniotomies. Yet, the acceptance of IoMRI is limited. OBJECTIVE: To evaluate impact of IoMRI on intracranial glioma resection outcome including overall patient survival. METHODS: A retrospective review of records was performed on a cohort of 164 consecutive patients who underwent resection surgery for newly diagnosed intracranial gliomas either with or without IoMRI technology performed by 2 neurosurgeons in our center. Patient follow-up was at least 5 years. Extent of resection (EOR) was calculated using pre- and postoperative contrast-enhanced and T2-weighted MR-images. Adjusted analysis was performed to compare gross total resection (GTR), EOR, permanent surgery-associated neurologic deficit, and overall survival between the 2 groups. RESULTS: Overall median EOR was 92.1%, and 97.45% with IoMRI use and 89.9% without IoMRI, with crude (unadjusted) P < 0.005. GTR was achieved in 49.3% of IoMRI cases, versus in only 21.4% of no-IoMRI cases, P < 0.001. GTR achieved was more with the use of IoMRI among gliomas located in both eloquent and noneloquent brain areas, P = 0.017 and <0.001, respectively. Permanent surgery-associated neurologic deficit was not (statistically) more significant with no-IoMRI, P = 0.284 (13.8% vs. 6.7%). In addition, the IoMRI group had better 5-year overall survival, P < 0.001. CONCLUSION: This study shows that the use of IoMRI was associated with greater rates of EOR and GTR, and better overall 5-year survival in both eloquent brain areas located and non-eloquent brain areas located gliomas, with no increased risk of neurologic complication.

Meyer A, Lasso A, Ungi T, Fichtinger G. Live Ultrasound Volume Reconstruction using Scout Scanning. Proc SPIE Int Soc Opt Eng. 2015;9415.Abstract

INTRODUCTION: Ultrasound-guided interventions often necessitate scanning of deep-seated anatomical structures that may be hard to visualize. Visualization can be improved using reconstructed 3D ultrasound volumes. High-resolution 3D reconstruction of a large area during clinical interventions is challenging if the region of interest is unknown. We propose a two-stage scanning method allowing the user to perform quick low-resolution scouting followed by high-resolution live volume reconstruction. METHODS: Scout scanning is accomplished by stacking 2D tracked ultrasound images into a low-resolution volume. Then, within a region of interest defined in the scout scan, live volume reconstruction can be performed by continuous scanning until sufficient image density is achieved. We implemented the workflow as a module of the open-source 3D Slicer application, within the SlicerIGT extension and building on the PLUS toolkit. RESULTS: Scout scanning is performed in a few seconds using 3 mm spacing to allow region of interest definition. Live reconstruction parameters are set to provide good image quality (0.5 mm spacing, hole filling enabled) and feedback is given during live scanning by regularly updated display of the reconstructed volume. DISCUSSION: Use of scout scanning may allow the physician to identify anatomical structures. Subsequent live volume reconstruction in a region of interest may assist in procedures such as targeting needle interventions or estimating brain shift during surgery.

Balasubramanian M, Mulkern RV, Wells III WM, Sundaram P, Orbach DB. Magnetic Resonance Imaging of Ionic Currents in Solution: The Effect of Magnetohydrodynamic Flow. Magn Reson Med. 2015;74 (4) :1145-55.Abstract

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

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.

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