Publications

2019
Inês Machado, Matthew Toews, Elizabeth George, Prashin Unadkat, Walid Essayed, Jie Luo, Pedro Teodoro, Herculano Carvalho, Jorge Martins, Polina Golland, Steve Pieper, Sarah Frisken, Alexandra Golby, William Wells, and Yangming Ou. 2019. “Deformable MRI-Ultrasound Registration using Correlation-based Attribute Matching for Brain Shift Correction: Accuracy and Generality in Multi-site Data.” Neuroimage, 202, Pp. 116094.Abstract
Intraoperative tissue deformation, known as brain shift, decreases the benefit of using preoperative images to guide neurosurgery. Non-rigid registration of preoperative magnetic resonance (MR) to intraoperative ultrasound (US) has been proposed as a means to compensate for brain shift. We focus on the initial registration from MR to predurotomy US. We present a method that builds on previous work to address the need for accuracy and generality of MR-iUS registration algorithms in multi-site clinical data. To improve accuracy of registration, we use high-dimensional texture attributes instead of image intensities and propose to replace the standard difference-based attribute matching with correlation-based attribute matching. We also present a strategy that deals explicitly with the large field-of-view mismatch between MR and iUS images. We optimize key parameters across independent MR-iUS brain tumor datasets acquired at three different institutions, with a total of 43 tumor patients and 758 corresponding landmarks to validate the registration algorithm. Despite differences in imaging protocols, patient demographics and landmark distributions, our algorithm was able to reduce landmark errors prior to registration in three data sets (5.37 ± 4.27, 4.18 ± 1.97 and 6.18 ± 3.38 mm, respectively) to a consistently low level (2.28 ± 0.71, 2.08 ± 0.37 and 2.24 ± 0.78 mm, respectively). Our algorithm is compared to 15 other algorithms that have been previously tested on MR-iUS registration and it is competitive with the state-of-the-art on multiple datasets. We show that our algorithm has one of the lowest errors in all datasets (accuracy), and this is achieved while sticking to a fixed set of parameters for multi-site data (generality). In contrast, other algorithms/tools of similar performance need per-dataset parameter tuning (high accuracy but lower generality), and those that stick to fixed parameters have larger errors or inconsistent performance (generality but not the top accuracy). We further characterized landmark errors according to brain regions and tumor types, a topic so far missing in the literature. We found that landmark errors were higher in high-grade than low-grade glioma patients, and higher in tumor regions than in other brain regions.
Sanjay S Yengul, Paul E Barbone, and Bruno Madore. 2019. “Dispersion in Tissue-Mimicking Gels Measured with Shear Wave Elastography and Torsional Vibration Rheometry.” Ultrasound Med Biol, 45, 2, Pp. 586-604.Abstract
Dispersion, or the frequency dependence of mechanical parameters, is a primary confounding factor in elastography comparisons. We present a study of dispersion in tissue-mimicking gels over a wide frequency band using a combination of ultrasound shear wave elastography (SWE), and a novel torsional vibration rheometry which allows independent mechanical measurement of SWE samples. Frequency-dependent complex shear modulus was measured in homogeneous gelatin hydrogels of two different bloom strengths while controlling for confounding factors such as temperature, water content and material aging. Furthermore, both techniques measured the same physical samples, thereby eliminating possible variation caused by batch-to-batch gel variation, sample geometry differences and boundary artifacts. The wide-band measurement, from 1 to 1800 Hz, captured a 30%-50% increase in the storage modulus and a nearly linear increase with frequency of the loss modulus. The magnitude of the variation suggests that accounting for dispersion is essential for meaningful comparisons between SWE implementations.
Martin T King, Paul L Nguyen, Ninjin Boldbaatar, David D Yang, Vinayak Muralidhar, Clare M Tempany, Robert A Cormack, Mark D Hurwitz, Warren W Suh, Mark M Pomerantz, Anthony V D'Amico, and Peter F Orio. 2019. “Evaluating the Influence of Prostate-specific Antigen Kinetics on Metastasis in Men with PSA Recurrence after Partial Gland Therapy.” Brachytherapy, 18, 2, Pp. 198-203.Abstract
PURPOSE: Although current Delphi Consensus guidelines do not recommend a specific definition of biochemical recurrence after partial gland therapy, these guidelines acknowledge that serial prostate-specific antigen (PSA) tests remain the best marker for monitoring disease after treatment. The purpose of this study was to determine whether PSA velocity at failure per the Phoenix (nadir + 2 ng/mL) definition is associated with metastasis and prostate cancer-specific mortality (PCSM) in a cohort of patients who experienced PSA failure after partial gland therapy. METHODS: Between 1997 and 2007, 285 patients with favorable risk prostate cancer underwent partial prostate brachytherapy to the peripheral zone. PSA velocity was calculated for 94 patients who experienced PSA failure per the Phoenix (nadir + 2) definition. Fine and Gray competing risks regression was performed to determine whether PSA velocity and other clinical factors were associated with metastasis and PCSM. RESULTS: The median time to PSA failure was 4.2 years (interquartile range: 2.2, 7.9), and the median followup time after PSA failure was 6.5 years (3.5-9.7). Seventeen patients developed metastases, and five experienced PCSM. On multivariate analysis, PSA velocity ≥3.0 ng/mL/year (adjusted hazard ratio 5.97; [2.57, 13.90]; p < 0.001) and PSA nadir (adjusted hazard ratio 0.39; [0.24, 0.64]; p < 0.001) were significantly associated with metastasis. PSA velocity ≥3.0 ng/mL/year was also associated with PCSM (HR 15.3; [1.8, 128.0]; p = 0.012) on univariate analysis. CONCLUSIONS: Rapid PSA velocity at PSA failure after partial gland treatment may be prognostic for long-term outcomes.
Paolo Zaffino, Guillaume Pernelle, Andre Mastmeyer, Alireza Mehrtash, Hongtao Zhang, Ron Kikinis, Tina Kapur, and Maria Francesca Spadea. 2019. “Fully Automatic Catheter Segmentation in MRI with 3D Convolutional Neural Networks: Application to MRI-guided Gynecologic Brachytherapy.” Phys Med Biol, 64, 16, Pp. 165008.Abstract
External-beam radiotherapy followed by High Dose Rate (HDR) brachytherapy is the standard-of-care for treating gynecologic cancers. The enhanced soft-tissue contrast provided by Magnetic Resonance Imaging (MRI) makes it a valuable imaging modality for diagnosing and treating these cancers. However, in contrast to Computed Tomography (CT) imaging, the appearance of the brachytherapy catheters, through which radiation sources are inserted to reach the cancerous tissue later on, is often variable across images. This paper reports, for the first time, a new deep-learning-based method for fully automatic segmentation of multiple closely spaced brachytherapy catheters in intraoperative MRI. &#13; Represented in the data are 50 gynecologic cancer patients treated by MRI-guided HDR brachytherapy. For each patient, a single intraoperative MRI was used. 826 catheters in the images were manually segmented by an expert radiation physicist who is also a trained radiation oncologist. The number of catheters in a patient ranged between 10 and 35. A deep 3-dimensional Convolutional Neural Network (CNN) model was developed and trained. In order to make the learning process more robust, the network was trained 5 times, each time using a different combination of shown patients. Finally, each test case was processed by the 5 networks and the final segmentation was generated by voting on the obtained 5 candidate segmentations. 4-fold validation was executed and all the patients were segmented.&#13; An average distance error of 2.0±3.4 mm was achieved. False positive and false negative catheters were 6.7% and 1.5% respectively. Average Dice score was equal to 0.60±0.17. The algorithm is available for use in the open source software platform 3D Slicer allowing for wide scale testing and research discussion. In conclusion, to the best of our knowledge, fully automatic segmentation of multiple closely spaced catheters from intraoperative MR images was achieved for the first time in gynecological brachytherapy.
Prashin Unadkat, Luca Fumagalli, Laura Rigolo, Mark G Vangel, Geoffrey S Young, Raymond Huang, Srinivasan Mukundan, Alexandra Golby, and Yanmei Tie. 2019. “Functional MRI Task Comparison for Language Mapping in Neurosurgical Patients.” J Neuroimaging, 29, 3, Pp. 348-56.Abstract
BACKGROUND AND PURPOSE: Language task-based functional MRI (fMRI) is increasingly used for presurgical planning in patients with brain lesions. Different paradigms elicit activations of different components of the language network. The aim of this study is to optimize fMRI clinical usage by comparing the effectiveness of three language tasks for language lateralization and localization in a large group of patients with brain lesions. METHODS: We analyzed fMRI data from a sequential retrospective cohort of 51 patients with brain lesions who underwent presurgical fMRI language mapping. We compared the effectiveness of three language tasks (Antonym Generation, Sentence Completion (SC), and Auditory Naming) for lateralizing language function and for activating cortex within patient-specific regions-of-interest representing eloquent language areas, and assessed the degree of spatial overlap of the areas of activation elicited by each task. RESULTS: The tasks were similarly effective for lateralizing language within the anterior language areas. The SC task produced higher laterality indices within the posterior language areas and had a significantly higher agreement with the clinical report. Dice coefficients between the task pairs were in the range of .351-.458, confirming substantial variation in the components of the language network activated by each task. CONCLUSIONS: SC task consistently produced large activations within the dominant hemisphere and was more effective for lateralizing language within the posterior language areas. The low degree of spatial overlap among the tasks strongly supports the practice of using a battery of tasks to help the surgeon to avoid eloquent language areas.
Nicholas D Schmitt, Catherine M Rawlins, Elizabeth C Randall, Xianzhe Wang, Antonius Koller, Jared R. Auclair, Jane-Marie Kowalski, Paul J. Kowalski, Ed Luther, Alexander R Ivanov, Nathalie YR Agar, and Jeffrey N Agar. 2019. “Genetically Encoded Fluorescent Proteins Enable High-Throughput Assignment of Cell Cohorts Directly from MALDI-MS Images.” Anal Chem, 91, 6, Pp. 3810-7.Abstract
Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) provides a unique in situ chemical profile that can include drugs, nucleic acids, metabolites, lipids, and proteins. MSI of individual cells (of a known cell type) affords a unique insight into normal and disease-related processes and is a prerequisite for combining the results of MSI and other single-cell modalities (e.g. mass cytometry and next-generation sequencing). Technological barriers have prevented the high-throughput assignment of MSI spectra from solid tissue preparations to their cell type. These barriers include obtaining a suitable cell-identifying image (e.g. immunohistochemistry) and obtaining sufficiently accurate registration of the cell-identifying and MALDI-MS images. This study introduces a technique that overcame these barriers by assigning cell type directly from mass spectra. We hypothesized that, in MSI from mice with a defined fluorescent protein expression pattern, the fluorescent protein's molecular ion could be used to identify cell cohorts. A method was developed for the purification of enhanced yellow fluorescent protein (EYFP) from mice. To determine EYFP's molecular mass for MSI studies, we performed intact mass analysis and characterized the protein's primary structure and post-translational modifications through various techniques. MALDI-MSI methods were developed to enhance the detection of EYFP in situ, and by extraction of EYFP's molecular ion from MALDI-MS images, automated, whole-image assignment of cell cohorts was achieved. This method was validated using a well-characterized mouse line that expresses EYFP in motor and sensory neurons and should be applicable to hundreds of commercially available mice (and other animal) strains comprising a multitude of cell-specific fluorescent labels.
Colles Price, Stanley Gill, Zandra V Ho, Shawn M Davidson, Erin Merkel, James M McFarland, Lisa Leung, Andrew Tang, Maria Kost-Alimova, Aviad Tsherniak, Oliver Jonas, Francisca Vazquez, and William C Hahn. 2019. “Genome-Wide Interrogation of Human Cancers Identifies EGLN1 Dependency in Clear Cell Ovarian Cancers.” Cancer Res, 79, 10, Pp. 2564-79.Abstract
We hypothesized that candidate dependencies for which there are small molecules that are either approved or in advanced development for a nononcology indication may represent potential therapeutic targets. To test this hypothesis, we performed genome-scale loss-of-function screens in hundreds of cancer cell lines. We found that knockout of , which encodes prolyl hydroxylase domain-containing protein 2 (PHD2), reduced the proliferation of a subset of clear cell ovarian cancer cell lines . EGLN1-dependent cells exhibited sensitivity to the pan-EGLN inhibitor FG-4592. The response to FG-4592 was reversed by deletion of HIF1A, demonstrating that EGLN1 dependency was related to negative regulation of HIF1A. We also found that ovarian clear cell tumors susceptible to both genetic and pharmacologic inhibition of EGLN1 required intact HIF1A. Collectively, these observations identify EGLN1 as a cancer target with therapeutic potential. SIGNIFICANCE: These findings reveal a differential dependency of clear cell ovarian cancers on EGLN1, thus identifying EGLN1 as a potential therapeutic target in clear cell ovarian cancer patients.
Wei Huang, Yiyi Chen, Andriy Fedorov, Xia Li, Guido H Jajamovich, Dariya I Malyarenko, Madhava P Aryal, Peter S LaViolette, Matthew J Oborski, Finbarr O'Sullivan, Richard G Abramson, Kourosh Jafari-Khouzani, Aneela Afzal, Alina Tudorica, Brendan Moloney, Sandeep N Gupta, Cecilia Besa, Jayashree Kalpathy-Cramer, James M Mountz, Charles M Laymon, Mark Muzi, Paul E Kinahan, Kathleen Schmainda, Yue Cao, Thomas L Chenevert, Bachir Taouli, Thomas E Yankeelov, Fiona Fennessy, and Xin Li. 2019. “The Impact of Arterial Input Function Determination Variations on Prostate Dynamic Contrast-Enhanced Magnetic Resonance Imaging Pharmacokinetic Modeling: A Multicenter Data Analysis Challenge, Part II.” Tomography, 5, 1, Pp. 99-109.Abstract
This multicenter study evaluated the effect of variations in arterial input function (AIF) determination on pharmacokinetic (PK) analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data using the shutter-speed model (SSM). Data acquired from eleven prostate cancer patients were shared among nine centers. Each center used a site-specific method to measure the individual AIF from each data set and submitted the results to the managing center. These AIFs, their reference tissue-adjusted variants, and a literature population-averaged AIF, were used by the managing center to perform SSM PK analysis to estimate K (volume transfer rate constant), v (extravascular, extracellular volume fraction), k (efflux rate constant), and τ (mean intracellular water lifetime). All other variables, including the definition of the tumor region of interest and precontrast T values, were kept the same to evaluate parameter variations caused by variations in only the AIF. Considerable PK parameter variations were observed with within-subject coefficient of variation (wCV) values of 0.58, 0.27, 0.42, and 0.24 for K, v, k, and τ, respectively, using the unadjusted AIFs. Use of the reference tissue-adjusted AIFs reduced variations in K and v (wCV = 0.50 and 0.10, respectively), but had smaller effects on k and τ (wCV = 0.39 and 0.22, respectively). k is less sensitive to AIF variation than K, suggesting it may be a more robust imaging biomarker of prostate microvasculature. With low sensitivity to AIF uncertainty, the SSM-unique τ parameter may have advantages over the conventional PK parameters in a longitudinal study.
Mehdi Taghipour, Alireza Ziaei, Francesco Alessandrino, Elmira Hassanzadeh, Mukesh Harisinghani, Mark Vangel, Clare M Tempany, and Fiona M Fennessy. 2019. “Investigating the Role of DCE-MRI, over T2 and DWI, in accurate PI-RADS v2 Assessment of Clinically Significant Peripheral Zone Prostate Lesions as Defined at Radical Prostatectomy.” Abdom Radiol (NY), 44, 4, Pp. 1520-7.Abstract
PURPOSE: PI-RADS v2 dictates that dynamic contrast-enhanced (DCE) imaging be used to further classify peripheral zone (PZ) cases that receive a diffusion-weighted imaging equivocal score of three (DWI3), a positive DCE resulting in an increase in overall assessment score to a four, indicative of clinically significant prostate cancer (csPCa). However, the accuracy of DCE in predicting csPCa in DWI3 PZ cases is unknown. This study sought to determine the frequency with which DCE changes the PI-RADS v2 DWI3 assessment category, and to determine the overall accuracy of DCE-MRI in equivocal PZ DWI3 lesions. MATERIALS AND METHODS: This is a retrospective study of patients with pathologically proven PCa who underwent prostate mpMRI at 3T and subsequent radical prostatectomy. PI-RADS v2 assessment categories were determined by a radiologist, aware of a diagnosis of PCa, but blinded to final pathology. csPCa was defined as a Gleason score ≥ 7 or extra prostatic extension at pathology review. Performance characteristics and diagnostic accuracy of DCE in assigning a csPCa assessment in PZ lesions were calculated. RESULTS: A total of 271 men with mean age of 59 ± 6 years mean PSA 6.7 ng/mL were included. csPCa was found in 212/271 (78.2%) cases at pathology, 209 of which were localized in the PZ. DCE was necessary to further classify (45/209) of patients who received a score of DWI3. DCE was positive in 29/45 cases, increasing the final PI-RADS v2 assessment category to a category 4, with 16/45 having a negative DCE. When compared with final pathology, DCE was correct in increasing the assessment category in 68.9% ± 7% (31/45) of DWI3 cases. CONCLUSION: DCE increases the accuracy of detection of csPCa in the majority of PZ lesions that receive an equivocal PI-RADS v2 assessment category using DWI.
Sankha S Basu, Madison H McMinn, Begoña Giménez-Cassina Lopéz, Michael S Regan, Elizabeth C Randall, Amanda R Clark, Christopher R Cox, and Nathalie YR Agar. 2019. “Metal Oxide Laser Ionization Mass Spectrometry Imaging (MOLI MSI) Using Cerium(IV) Oxide.” Anal Chem, 91, 10, Pp. 6800-7.Abstract
Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a powerful technique for spatially resolved metabolomics. A variation on MALDI, termed metal oxide laser ionization (MOLI), capitalizes on the unique property of cerium(IV) oxide (CeO) to induce laser-catalyzed fatty acyl cleavage from lipids and has been utilized for bacterial identification. In this study, we present the development and utilization of CeO as an MSI catalyst. The method was developed using a MALDI TOF instrument in negative ion mode, equipped with a high frequency laser. Instrument parameters for MOLI MS fatty acid catalysis with CeO were optimized with phospholipid standards and fatty acid catalysis was confirmed using lipid extracts from reference bacterial strains, and sample preparation was optimized using mouse brain tissue. MOLI MSI was applied to the imaging of normal mouse brain revealing differentiable fatty acyl pools in myelinated and nonmyelinated regions. Similarly, MOLI MSI showed distinct fatty acyl composition in tumor regions of a patient derived xenograft mouse model of glioblastoma. To assess the potential of MOLI MSI to detect pathogens directly from tissue, a pseudoinfection model was prepared by spotting Escherichia coli lipid extracts on mouse brain tissue sections and imaged by MOLI MSI. The spotted regions were molecularly resolved from the supporting mouse brain tissue by the diagnostic odd-chained fatty acids and reflected control bacterial MOLI MS signatures. We describe MOLI MSI for the first time and highlight its potential for spatially resolved fatty acyl analysis, characterization of fatty acyl composition in tumors, and its potential for pathogen detection directly from tissue.
Fan Zhang, Lipeng Ning, Lauren J O'Donnell, and Ofer Pasternak. 2019. “MK-curve - Characterizing the Relation between Mean Kurtosis and Alterations in the Diffusion MRI Signal.” Neuroimage, 196, Pp. 68-80.Abstract
Diffusion kurtosis imaging (DKI) is a diffusion MRI (dMRI) technique to quantify brain microstructural properties. While DKI measures are sensitive to tissue alterations, they are also affected by signal alterations caused by imaging artifacts such as noise, motion and Gibbs ringing. Consequently, DKI often yields output parameter values (e.g. mean kurtosis; MK) that are implausible. These include implausible values that are outside of the range dictated by physics/biology, and visually apparent implausible values that form unexpected discontinuities, being too high or too low comparing with their neighborhood. These implausible values will introduce bias into any following data analyses (e.g. between-population statistical computation). Existing studies have attempted to correct implausible DKI parameter values in multiple ways; however, these approaches are not always effective. In this study, we propose a novel method for detecting and correcting voxels with implausible values to enable improved DKI parameter estimation. In particular, we focus on MK parameter estimation. We first characterize the relation between MK and alterations in the dMRI signal including diffusion weighted images (DWIs) and the baseline (b0) images. This is done by calculating MK for a range of synthetic DWI or b0 for each voxel, and generating curves (MK-curve) representing how alterations to the input dMRI signals affect the resulting output MK. We find that voxels with implausible MK values are more likely caused by artifacts in the b0 images than artifacts in DWIs with higher b-values. Accordingly, two characteristic b0 values, which define a range of synthetic b0 values that generate implausible MK values, are identified on the MK-curve. Based on this characterization, we propose an automatic approach for detection of voxels with implausible MK values by comparing a voxel's original b0 signal to the identified two characteristic b0 values, along with a correction strategy to replace the original b0 in each detected implausible voxel with a synthetic b0 value computed from the MK-curve. We evaluate the method on a DKI phantom dataset and dMRI datasets from the Human Connectome Project (HCP), and we compare the proposed correction method with other previously proposed correction methods. Results show that our proposed method is able to identify and correct most voxels with implausible DKI parameter values as well as voxels with implausible diffusion tensor parameter values.
Elizabeth C Randall, Giorgia Zadra, Paolo Chetta, Begona GC Lopez, Sudeepa Syamala, Sankha S Basu, Jeffrey N Agar, Massimo Loda, Clare M Tempany, Fiona M Fennessy, and Nathalie YR Agar. 2019. “Molecular Characterization of Prostate Cancer with Associated Gleason Score using Mass Spectrometry Imaging.” Mol Cancer Res, 17, 5, Pp. 1155-65.Abstract
Diagnosis of prostate cancer is based on histological evaluation of tumor architecture using a system known as the 'Gleason score'. This diagnostic paradigm, while the standard of care, is time-consuming, shows intra-observer variability and provides no information about the altered metabolic pathways, which result in altered tissue architecture. Characterization of the molecular composition of prostate cancer and how it changes with respect to the Gleason score (GS) could enable a more objective and faster diagnosis. It may also aid in our understanding of disease onset and progression. In this work, we present mass spectrometry imaging for identification and mapping of lipids and metabolites in prostate tissue from patients with known prostate cancer with GS from 6 to 9. A gradient of changes in the intensity of various lipids was observed, which correlated with increasing GS. Interestingly, these changes were identified in both regions of high tumor cell density, and in regions of tissue that appeared histologically benign, possibly suggestive of pre-cancerous metabolomic changes. A total of 31 lipids, including several phosphatidylcholines, phosphatidic acids, phosphatidylserines, phosphatidylinositols and cardiolipins were detected with higher intensity in GS (4+3) compared with GS (3+4), suggesting they may be markers of prostate cancer aggression. Results obtained through mass spectrometry imaging studies were subsequently correlated with a fast, ambient mass spectrometry method for potential use as a clinical tool to support image-guided prostate biopsy. Implications: In this study we suggest that metabolomic differences between prostate cancers with different Gleason scores can be detected by mass spectrometry imaging.
Ananya Panda, Verena C Obmann, Wei-Ching Lo, Seunghee Margevicius, Yun Jiang, Mark Schluchter, Indravadan J Patel, Dean Nakamoto, Chaitra Badve, Mark A Griswold, Irina Jaeger, Lee E Ponsky, and Vikas Gulani. 2019. “MR Fingerprinting and ADC Mapping for Characterization of Lesions in the Transition Zone of the Prostate Gland.” Radiology, 292, 3, Pp. 685-94.Abstract
BackgroundPreliminary studies have shown that MR fingerprinting-based relaxometry combined with apparent diffusion coefficient (ADC) mapping can be used to differentiate normal peripheral zone from prostate cancer and prostatitis. The utility of relaxometry and ADC mapping for the transition zone (TZ) is unknown.PurposeTo evaluate the utility of MR fingerprinting combined with ADC mapping for characterizing TZ lesions.Materials and MethodsTZ lesions that were suspicious for cancer in men who underwent MRI with T2-weighted imaging and ADC mapping ( values, 50-1400 sec/mm), MR fingerprinting with steady-state free precession, and targeted biopsy (60 in-gantry and 15 cognitive targeting) between September 2014 and August 2018 in a single university hospital were retrospectively analyzed. Two radiologists blinded to Prostate Imaging Reporting and Data System (PI-RADS) scores and pathologic diagnosis drew regions of interest on cancer-suspicious lesions and contralateral visually normal TZs (NTZs) on MR fingerprinting and ADC maps. Linear mixed models compared two-reader means of T1, T2, and ADC. Generalized estimating equations logistic regression analysis was used to evaluate both MR fingerprinting and ADC in differentiating NTZ, cancers and noncancers, clinically significant (Gleason score ≥ 7) cancers from clinically insignificant lesions (noncancers and Gleason 6 cancers), and characterizing PI-RADS version 2 category 3 lesions.ResultsIn 67 men (mean age, 66 years ± 8 [standard deviation]) with 75 lesions, targeted biopsy revealed 37 cancers (six PI-RADS category 3 cancers and 31 PI-RADS category 4 or 5 cancers) and 38 noncancers (31 PI-RADS category 3 lesions and seven PI-RADS category 4 or 5 lesions). The T1, T2, and ADC of NTZ (1800 msec ± 150, 65 msec ± 22, and [1.13 ± 0.19] × 10 mm/sec, respectively) were higher than those in cancers (1450 msec ± 110, 36 msec ± 11, and [0.57 ± 0.13] × 10 mm/sec, respectively; < .001 for all). The T1, T2, and ADC in cancers were lower than those in noncancers (1620 msec ± 120, 47 msec ± 16, and [0.82 ± 0.13] × 10 mm/sec, respectively; = .001 for T1 and ADC and = .03 for T2). The area under the receiver operating characteristic curve (AUC) for T1 plus ADC was 0.94 for separation. T1 and ADC in clinically significant cancers (1440 msec ± 140 and [0.58 ± 0.14] × 10 mm/sec, respectively) were lower than those in clinically insignificant lesions (1580 msec ± 120 and [0.75 ± 0.17] × 10 mm/sec, respectively; = .001 for all). The AUC for T1 plus ADC was 0.81 for separation. Within PI-RADS category 3 lesions, T1 and ADC of cancers (1430 msec ± 220 and [0.60 ± 0.17] × 10 mm/sec, respectively) were lower than those of noncancers (1630 msec ± 120 and [0.81 ± 0.13] × 10 mm/sec, respectively; = .006 for T1 and = .004 for ADC). The AUC for T1 was 0.79 for differentiating category 3 lesions.ConclusionMR fingerprinting-based relaxometry combined with apparent diffusion coefficient mapping may improve transition zone lesion characterization.© RSNA, 2019
JP Guenette, N Ben-Shlomo, J Jayender, RT Seethamraju, V Kimbrell, N-A Tran, RY Huang, CJ Kim, JI Kass, CE Corrales, and TC Lee. 2019. “MR Imaging of the Extracranial Facial Nerve with the CISS Sequence.” AJNR Am J Neuroradiol, 40, 11, Pp. 1954-9.Abstract
BACKGROUND AND PURPOSE: MR imaging is not routinely used to image the extracranial facial nerve. The purpose of this study was to determine the extent to which this nerve can be visualized with a CISS sequence and to determine the feasibility of using that sequence for locating the nerve relative to tumor. MATERIALS AND METHODS: Thirty-two facial nerves in 16 healthy subjects and 4 facial nerves in 4 subjects with parotid gland tumors were imaged with an axial CISS sequence protocol that included 0.8-mm isotropic voxels on a 3T MR imaging system with a 64-channel head/neck coil. Four observers independently segmented the 32 healthy subject nerves. Segmentations were compared by calculating average Hausdorff distance values and Dice similarity coefficients. RESULTS: The primary bifurcation of the extracranial facial nerve into the superior temporofacial and inferior cervicofacial trunks was visible on all 128 segmentations. The mean of the average Hausdorff distances was 1.2 mm (range, 0.3-4.6 mm). Dice coefficients ranged from 0.40 to 0.82. The relative position of the facial nerve to the tumor could be inferred in all 4 tumor cases. CONCLUSIONS: The facial nerve can be seen on CISS images from the stylomastoid foramen to the temporofacial and cervicofacial trunks, proximal to the parotid plexus. Use of a CISS protocol is feasible in the clinical setting to determine the location of the facial nerve relative to tumor.
Jean-Jacques Lemaire, Antonio De Salles, Guillaume Coll, Youssef El Ouadih, Rémi Chaix, Jérôme Coste, Franck Durif, Nikos Makris, and Ron Kikinis. 2019. “MRI Atlas of the Human Deep Brain.” Front Neurol, 10, Pp. 851.Abstract
Mastering detailed anatomy of the human deep brain in clinical neurosciences is challenging. Although numerous pioneering works have gathered a large dataset of structural and topographic information, it is still difficult to transfer this knowledge into practice, even with advanced magnetic resonance imaging techniques. Thus, classical histological atlases continue to be used to identify structures for stereotactic targeting in functional neurosurgery. Physicians mainly use these atlases as a template co-registered with the patient's brain. However, it is possible to directly identify stereotactic targets on MRI scans, enabling personalized targeting. In order to help clinicians directly identify deep brain structures relevant to present and future medical applications, we built a volumetric MRI atlas of the deep brain (MDBA) on a large scale (infra millimetric). Twelve hypothalamic, 39 subthalamic, 36 telencephalic, and 32 thalamic structures were identified, contoured, and labeled. Nineteen coronal, 18 axial, and 15 sagittal MRI plates were created. Although primarily designed for direct labeling, the anatomic space was also subdivided in twelfths of AC-PC distance, leading to proportional scaling in the coronal, axial, and sagittal planes. This extensive work is now available to clinicians and neuroscientists, offering another representation of the human deep brain ([https://hal.archives-ouvertes.fr/] [hal-02116633]). The atlas may also be used by computer scientists who are interested in deciphering the topography of this complex region.
Muna Aryal, Iason Papademetriou, Yong-Zhi Zhang, Chanikarn Power, Nathan McDannold, and Tyrone Porter. 2019. “MRI Monitoring and Quantification of Ultrasound-Mediated Delivery of Liposomes Dually Labeled with Gadolinium and Fluorophore through the Blood-Brain Barrier.” Ultrasound Med Biol, 45, 7, Pp. 1733-42.Abstract
Magnetic resonance image-guided focused ultrasound has emerged as a viable non-invasive technique for the treatment of central nervous system-related diseases/disorders. Application of mechanical and thermal effects associated with focused transcranial ultrasound has been studied extensively in pre-clinical models, which has paved the way for clinical trials. However, in vivo treatment evaluation techniques on drug delivery application via blood-brain barrier opening has not been fully explored. Current treatment evaluation techniques via magnetic resonance imaging are hindered by systemic toxicity resulting from free gadolinium delivery. Here we propose a novel treatment evaluation strategy to overcome limitations by (i) synthesizing liposomes that are dually labeled with gadolinium, a magnetic resonance imaging (MRI) contrast agent, and rhodamine, a fluorophore; (ii) applying a focused ultrasound (FUS)-mediated BBB opening technique to deliver the liposomes across vascular barriers, achieving local gadolinium enhancement while reducing systemic and unwanted regional toxic effects associated with free gadolinium; and (iii) utilizing the MRI modality to confirm the delivery as it is already included in the FUS treatment in clinic. Liposomes were secondarily labeled with a fluorescent marker to confirm results obtained by MRI quantification postmortem. Two different sizes, 77.5 nm (group A) and 140 nm (group B), of gadolinium- and fluorescence-labeled liposomes were fabricated using thin-film hydration followed by extrusion methods and determined their stability up to 6 h under physiologic conditions. Gadolinium signal was detected on contrast-enhanced T1-weighted MRI 5 h after the delivery of liposomes via the BBB opening approach with an ultrasound pulse of 0.42 MPa (estimate in water) combined with microbubbles. MRI contrast was enhanced significantly in sonicated regions compared with non-sonicated regions of the brain. This was due to the accumulation of labeled liposomes, which was confirmed by detection of rhodamine fluorescence in histologic sections. The relative increase in MRI signal intensity was greater for smaller liposomes (mean diameter = 77.5 nm) than larger liposomes (mean diameter = 140 nm), which suggested a greater accumulation of the smaller liposomes in the brain after ultrasound-mediated opening of the BBB. Our findings suggest that the dual-labeled nanocarrier platform can be established, the FUS-mediated BBB opening approach can be used to deliver it through vascular barriers and MRI can be used to evaluate the extent of nanocarrier delivery.
Thomas C Lee, Jeffrey P Guenette, Ziev B Moses, and John H Chi. 2019. “MRI-Guided Cryoablation of Epidural Malignancies in the Spinal Canal Resulting in Neural Decompression and Regrowth of Bone.” AJR Am J Roentgenol, 212, 1, Pp. 205-8.Abstract
OBJECTIVE: The purpose of this article is to describe the use of MRI to safely monitor cryoablation for the treatment of spinal epidural malignancies. CONCLUSION: Use of MRI guidance to monitor percutaneous cryoablation allows ablation margins more distinct than those allowed by heat-based ablation modalities. MRI-guided cryoablation is a feasible option for treating epidural tumors involving the spinal canal, resulting in successful decompression of the tumor away from the spinal cord with regrowth of previously eroded bone around the spinal canal.
Cheng-Chieh Cheng, Frank Preiswerk, W. Scott Hoge, Tai-Hsin Kuo, and Bruno Madore. 2019. “Multipathway Multi-echo (MPME) Imaging: All Main MR Parameters Mapped Based on a Single 3D Scan.” Magn Reson Med, 81, 3, Pp. 1699-1713.Abstract
PURPOSE: Quantitative parameter maps, as opposed to qualitative grayscale images, may represent the future of diagnostic MRI. A new quantitative MRI method is introduced here that requires a single 3D acquisition, allowing good spatial coverage to be achieved in relatively short scan times. METHODS: A multipathway multi-echo sequence was developed, and at least 3 pathways with 2 TEs were needed to generate T , T , T , B , and B maps. The method required the central k-space region to be sampled twice, with the same sequence but with 2 very different nominal flip angle settings. Consequently, scan time was only slightly longer than that of a single scan. The multipathway multi-echo data were reconstructed into parameter maps, for phantom as well as brain acquisitions, in 5 healthy volunteers at 3 T. Spatial resolution, matrix size, and FOV were 1.2 × 1.0 × 1.2 mm , 160 × 192 × 160, and 19.2 × 19.2 × 19.2 cm (whole brain), acquired in 11.5 minutes with minimal acceleration. Validation was performed against T , T , and T maps calculated from gradient-echo and spin-echo data. RESULTS: In Bland-Altman plots, bias and limits of agreement for T and T results in vivo and in phantom were -2.9/±125.5 ms (T in vivo), -4.8/±20.8 ms (T in vivo), -1.5/±18.1 ms (T in phantom), and -5.3/±7.4 ms (T in phantom), for regions of interest including given brain structures or phantom compartments. Due to relatively high noise levels, the current implementation of the approach may prove more useful for region of interest-based as opposed to pixel-based interpretation. CONCLUSIONS: We proposed a novel approach to quantitatively map MR parameters based on a multipathway multi-echo acquisition.
Sonja Stojanovski, Daniel Felsky, Joseph D Viviano, Saba Shahab, Rutwik Bangali, Christie L Burton, Gabriel A Devenyi, Lauren J O'Donnell, Peter Szatmari, Mallar M Chakravarty, Stephanie Ameis, Russell Schachar, Aristotle N Voineskos, and Anne L Wheeler. 2019. “Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury.” Biol Psychiatry, 85, 5, Pp. 408-16.Abstract
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a major sequela of traumatic brain injury (TBI) in youths. The objective of this study was to examine whether ADHD symptoms are differentially associated with genetic risk and brain structure in youths with and without a history of TBI. METHODS: Medical history, ADHD symptoms, genetic data, and neuroimaging data were obtained from a community sample of youths. ADHD symptom severity was compared between those with and without TBI (TBI n = 418, no TBI n = 3193). The relationship of TBI history, genetic vulnerability, brain structure, and ADHD symptoms was examined by assessing 1) ADHD polygenic score (discovery sample ADHD n = 19,099, control sample n = 34,194), 2) basal ganglia volumes, and 3) fractional anisotropy in the corpus callosum and corona radiata. RESULTS: Youths with TBI reported greater ADHD symptom severity compared with those without TBI. Polygenic score was positively associated with ADHD symptoms in youths without TBI but not in youths with TBI. The negative association between the caudate volume and ADHD symptoms was not moderated by a history of TBI. However, the relationship between ADHD symptoms and structure of the genu of the corpus callosum was negative in youths with TBI and positive in youths without TBI. CONCLUSIONS: The identification of distinct ADHD etiology in youths with TBI provides neurobiological insight into the clinical heterogeneity in the disorder. Results indicate that genetic predisposition to ADHD does not increase the risk for ADHD symptoms associated with TBI. ADHD symptoms associated with TBI may be a result of a mechanical insult rather than neurodevelopmental factors.
Di Fan, Nikhil N Chaudhari, Kenneth A Rostowsky, Maria Calvillo, Sean K Lee, Nahian F Chowdhury, Fan Zhang, Lauren J O'Donnell, and Andrei Irimia. 2019. “Post-Traumatic Cerebral Microhemorrhages and their Effects Upon White Matter Connectivity in the Aging Human Brain.” Conf Proc IEEE Eng Med Biol Soc, 2019, Pp. 198-203.Abstract
Cerebral microbleeds (CMBs), a common manifestation of mild traumatic brain injury (mTBI), have been sporadically implicated in the neurocognitive deficits of mTBI victims but their clinical significance has not been established adequately. Here we investigate the longitudinal effects of post-mTBI CMBs upon the fractional anisotropy (FA) of white matter (WM) in 21 older mTBI patients across the first ~6 months post-injury. CMBs were segmented automatically from susceptibility-weighted imaging (SWI) by leveraging the intensity gradient properties of SWI to identify CMB-related hypointensities using gradient-based edge detection. A detailed diffusion magnetic resonance imaging (dMRI) atlas of WM was used to segment and cluster tractography streamlines whose prototypes were then identified. The correlation coefficient was calculated between (A) FA values at vertices along streamline prototypes and (B) topological (along-streamline) distances between these vertices and the nearest CMB. Across subjects, the CMB identification approach achieved a sensitivity of 97.1% ± 4.7% and a precision of 72.4% ± 11.0% across subjects. The correlation coefficient was found to be negative and, additionally, statistically significant for 12.3% ± 3.5% of WM clusters (p <; 0.05, corrected), whose FA was found to decrease, on average, by 11.8% ± 5.3% across the first 6 months post-injury. These results suggest that CMBs can be associated with deleterious effects upon peri-lesional WM and highlight the vulnerability of older mTBI patients to neurovascular injury.

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