Publications

2020
Thomas C Lee, Jeffrey P Guenette, Ziev B Moses, Jong Woo Lee, Donald J Annino, and John H Chi. 10/2020. “MRI and CT Guided Cryoablation for Intracranial Extension of Malignancies along the Trigeminal Nerve.” J Neurol Surg B Skull Base, 81, 5, Pp. 511-514.Abstract
 To describe the technical aspects and early clinical outcomes of patients undergoing percutaneous magnetic resonance imaging (MRI)-guided tumor cryoablation along the intracranial trigeminal nerve. This study is a retrospective case review. Large academic tertiary care hospital. Patients who underwent MRI-guided cryoablation of perineural tumor along the intracranial trigeminal nerve. Technical success, pain relief, local control. Percutaneous MRI-guided cryoablation of tumor spread along the intracranial portion of the trigeminal nerve was performed in two patients without complication, with subsequent pain relief, and with local control in the patient with follow-up imaging. Percutaneous MRI-guided cryoablation is a feasible treatment option for malignancies tracking intracranially along the trigeminal nerve.
Fiona M Fennessy, Andriy Fedorov, Mark G Vangel, Robert V. Mulkern, Maria Tretiakova, Rosina T Lis, Clare Tempany, and Mary-Ellen Taplin. 10/2020. “Multiparametric MRI as a Biomarker of Response to Neoadjuvant Therapy for Localized Prostate Cancer-A Pilot Study.” Acad Radiol, 27, 10, Pp. 1432-9.Abstract
RATIONALE AND OBJECTIVES: To explore a role for multiparametric MRI (mpMRI) as a biomarker of response to neoadjuvant androgen deprivation therapy (ADT) for prostate cancer (PCa). MATERIALS AND METHODS: This prospective study was approved by the institutional review board and was HIPAA compliant. Eight patients with localized PCa had a baseline mpMRI, repeated after 6-months of ADT, followed by prostatectomy. mpMRI indices were extracted from tumor and normal regions of interest (TROI/NROI). Residual cancer burden (RCB) was measured on mpMRI and on the prostatectomy specimen. Paired t-tests compared TROI/NROI mpMRI indices and pre/post-treatment TROI mpMRI indices. Spearman's rank tested for correlations between MRI/pathology-based RCB, and between pathological RCB and mpMRI indices. RESULTS: At baseline, TROI apparent diffusion coefficient (ADC) was lower and dynamic contrast enhanced (DCE) metrics were higher, compared to NROI (ADC: 806 ± 137 × 10 vs. 1277 ± 213 × 10 mm/sec, p = 0.0005; K: 0.346 ± 0.16 vs. 0.144 ± 0.06 min, p = 0.002; AUC: 0.213 ± 0.08 vs. 0.11 ± 0.03, p = 0.002). Post-treatment, there was no change in TROI ADC, but a decrease in TROI K (0.346 ± 0.16 to 0.188 ± 0.08 min; p = 0.02) and AUC (0.213 ± 0.08 to 0.13 ± 0.06; p = 0.02). Tumor volume decreased with ADT. There was no difference between mpMRI-based and pathology-based RCB, which positively correlated (⍴ = 0.74-0.81, p < 0.05). Pathology-based RCB positively correlated with post-treatment DCE metrics (⍴ = 0.76-0.70, p < 0.05) and negatively with ADC (⍴ = -0.79, p = 0.03). CONCLUSION: Given the heterogeneity of PCa, an individualized approach to ADT may maximize potential benefit. This pilot study suggests that mpMRI may serve as a biomarker of ADT response and as a surrogate for RCB at prostatectomy.
Richard Jarrett Rushmore, Peter Wilson-Braun, George Papadimitriou, Isaac Ng, Yogesh Rathi, Fan Zhang, Lauren Jean O'Donnell, Marek Kubicki, Sylvain Bouix, Edward Yeterian, Jean-Jacques Lemaire, Evan Calabrese, Allan G Johnson, Ron Kikinis, and Nikos Makris. 9/2020. “3D Exploration of the Brainstem in 50-Micron Resolution MRI.” Front Neuroanat, 14, Pp. 40.Abstract
The brainstem, a structure of vital importance in mammals, is currently becoming a principal focus in cognitive, affective, and clinical neuroscience. Midbrain, pontine and medullary structures serve as the conduit for signals between the forebrain and spinal cord, are the epicenter of cranial nerve-circuits and systems, and subserve such integrative functions as consciousness, emotional processing, pain, and motivation. In this study, we parcellated the nuclear masses and the principal fiber pathways that were visible in a high-resolution T2-weighted MRI dataset of 50-micron isotropic voxels of a postmortem human brainstem. Based on this analysis, we generated a detailed map of the human brainstem. To assess the validity of our maps, we compared our observations with histological maps of traditional human brainstem atlases. Given the unique capability of MRI-based morphometric analysis in generating and preserving the morphology of 3D objects from individual 2D sections, we reconstructed the motor, sensory and integrative neural systems of the brainstem and rendered them in 3D representations. We anticipate the utilization of these maps by the neuroimaging community for applications in basic neuroscience as well as in neurology, psychiatry, and neurosurgery, due to their versatile computational nature in 2D and 3D representations in a publicly available capacity.
Nityanand Miskin, Prashin Unadkat, Michael E Carlton, Alexandra J Golby, Geoffrey S Young, and Raymond Y Huang. 8/2020. “Frequency and Evolution of New Postoperative Enhancement on 3 Tesla Intraoperative and Early Postoperative Magnetic Resonance Imaging.” Neurosurgery, 87, 2, Pp. 238-46.Abstract
BACKGROUND: Intraoperative magnetic resonance imaging (IO-MRI) provides real-time assessment of extent of resection of brain tumor. Development of new enhancement during IO-MRI can confound interpretation of residual enhancing tumor, although the incidence of this finding is unknown. OBJECTIVE: To determine the frequency of new enhancement during brain tumor resection on intraoperative 3 Tesla (3T) MRI. To optimize the postoperative imaging window after brain tumor resection using 1.5 and 3T MRI. METHODS: We retrospectively evaluated 64 IO-MRI performed for patients with enhancing brain lesions referred for biopsy or resection as well as a subset with an early postoperative MRI (EP-MRI) within 72 h of surgery (N = 42), and a subset with a late postoperative MRI (LP-MRI) performed between 120 h and 8 wk postsurgery (N = 34). Three radiologists assessed for new enhancement on IO-MRI, and change in enhancement on available EP-MRI and LP-MRI. Consensus was determined by majority response. Inter-rater agreement was assessed using percentage agreement. RESULTS: A total of 10 out of 64 (16%) of the IO-MRI demonstrated new enhancement. Seven of 10 patients with available EP-MRI demonstrated decreased/resolved enhancement. One out of 42 (2%) of the EP-MRI demonstrated new enhancement, which decreased on LP-MRI. Agreement was 74% for the assessment of new enhancement on IO-MRI and 81% for the assessment of new enhancement on the EP-MRI. CONCLUSION: New enhancement occurs in intraoperative 3T MRI in 16% of patients after brain tumor resection, which decreases or resolves on subsequent MRI within 72 h of surgery. Our findings indicate the opportunity for further study to optimize the postoperative imaging window.
Alireza Mehrtash, William M Wells, Clare M Tempany, Purang Abolmaesumi, and Tina Kapur. 7/2020. “Confidence Calibration and Predictive Uncertainty Estimation for Deep Medical Image Segmentation.” IEEE Trans Med Imaging.Abstract
Fully convolutional neural networks (FCNs), and in particular U-Nets, have achieved state-of-the-art results in semantic segmentation for numerous medical imaging applications. Moreover, batch normalization and Dice loss have been used successfully to stabilize and accelerate training. However, these networks are poorly calibrated i.e. they tend to produce overconfident predictions for both correct and erroneous classifications, making them unreliable and hard to interpret. In this paper, we study predictive uncertainty estimation in FCNs for medical image segmentation. We make the following contributions: 1) We systematically compare cross-entropy loss with Dice loss in terms of segmentation quality and uncertainty estimation of FCNs; 2)We propose model ensembling for confidence calibration of the FCNs trained with batch normalization and Dice loss; 3) We assess the ability of calibrated FCNs to predict segmentation quality of structures and detect out-of-distribution test examples. We conduct extensive experiments across three medical image segmentation applications of the brain, the heart, and the prostate to evaluate our contributions. The results of this study offer considerable insight into the predictive uncertainty estimation and out-of-distribution detection in medical image segmentation and provide practical recipes for confidence calibration. Moreover, we consistently demonstrate that model ensembling improves confidence calibration.
Adomas Bunevicius, Nathan Judson McDannold, and Alexandra J Golby. 7/2020. “Focused Ultrasound Strategies for Brain Tumor Therapy.” Oper Neurosurg (Hagerstown), 19, 1, Pp. 9-18.Abstract
BACKGROUND: A key challenge in the medical treatment of brain tumors is the limited penetration of most chemotherapeutic agents across the blood-brain barrier (BBB) into the tumor and the infiltrative margin around the tumor. Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising tool to enhance the delivery of chemotherapeutic agents into brain tumors. OBJECTIVE: To review the mechanism of FUS, preclinical evidence, and clinical studies that used low-frequency FUS for a BBB opening in gliomas. METHODS: Literature review. RESULTS: The potential of externally delivered low-intensity ultrasound for a temporally and spatially precise and predictable disruption of the BBB has been investigated for over a decade, yielding extensive preclinical literature demonstrating that FUS can disrupt the BBB in a spatially targeted and temporally reversible manner. Studies in animal models documented that FUS enhanced the delivery of numerous chemotherapeutic and investigational agents across the BBB and into brain tumors, including temozolomide, bevacizumab, 1,3-bis (2-chloroethyl)-1-nitrosourea, doxorubicin, viral vectors, and cells. Chemotherapeutic interventions combined with FUS slowed tumor progression and improved animal survival. Recent advances of MRgFUS systems allow precise, temporally and spatially controllable, and safe transcranial delivery of ultrasound energy. Initial clinical evidence in glioma patients has shown the efficacy of MRgFUS in disrupting the BBB, as demonstrated by an enhanced gadolinium penetration. CONCLUSION: Thus far, a temporary disruption of the BBB followed by the administration of chemotherapy has been both feasible and safe. Further studies are needed to determine the actual drug delivery, including the drug distribution at a tissue-level scale, as well as effects on tumor growth and patient prognosis.
James J Levitt, Paul G Nestor, Marek Kubicki, Amanda E Lyall, Fan Zhang, Tammy Riklin-Raviv, Lauren J O Donnell, Robert W McCarley, Martha E Shenton, and Yogesh Rathi. 7/2020. “Miswiring of Frontostriatal Projections in Schizophrenia.” Schizophr Bull, 8, 46, Pp. 990-8.Abstract
We investigated brain wiring in chronic schizophrenia and healthy controls in frontostriatal circuits using diffusion magnetic resonance imaging tractography in a novel way. We extracted diffusion streamlines in 27 chronic schizophrenia and 26 healthy controls connecting 4 frontal subregions to the striatum. We labeled the projection zone striatal surface voxels into 2 subtypes: dominant-input from a single cortical subregion, and, functionally integrative, with mixed-input from diverse cortical subregions. We showed: 1) a group difference for total striatal surface voxel number (P = .045) driven by fewer mixed-input voxels in the left (P  = .007), but not right, hemisphere; 2) a group by hemisphere interaction for the ratio quotient between voxel subtypes (P  = .04) with a left (P  = .006), but not right, hemisphere increase in schizophrenia, also reflecting fewer mixed-input voxels; and 3) fewer mixed-input voxel counts in schizophrenia (P  = .045) driven by differences in left hemisphere limbic (P  = .007) and associative (P  = .01), but not sensorimotor, striatum. These results demonstrate a less integrative pattern of frontostriatal structural connectivity in chronic schizophrenia. A diminished integrative pattern yields a less complex input pattern to the striatum from the cortex with less circuit integration at the level of the striatum. Further, as brain wiring occurs during early development, aberrant brain wiring could serve as a developmental biomarker for schizophrenia.
Fan Zhang, Guoqiang Xie, Laura Leung, Michael A Mooney, Lorenz Epprecht, Isaiah Norton, Yogesh Rathi, Ron Kikinis, Ossama Al-Mefty, Nikos Makris, Alexandra J Golby, and Lauren J O'Donnell. 6/2020. “Creation of a Novel Trigeminal Tractography Atlas for Automated Trigeminal Nerve Identification.” Neuroimage, 220, Pp. 117063.Abstract
Diffusion MRI (dMRI) tractography has been successfully used to study the trigeminal nerves (TGNs) in many clinical and research applications. Currently, identification of the TGN in tractography data requires expert nerve selection using manually drawn regions of interest (ROIs), which is prone to inter-observer variability, time-consuming and carries high clinical and labor costs. To overcome these issues, we propose to create a novel anatomically curated TGN tractography atlas that enables automated identification of the TGN from dMRI tractography. In this paper, we first illustrate the creation of a trigeminal tractography atlas. Leveraging a well-established computational pipeline and expert neuroanatomical knowledge, we generate a data-driven TGN fiber clustering atlas using tractography data from 50 subjects from the Human Connectome Project. Then, we demonstrate the application of the proposed atlas for automated TGN identification in new subjects, without relying on expert ROI placement. Quantitative and visual experiments are performed with comparison to expert TGN identification using dMRI data from two different acquisition sites. We show highly comparable results between the automatically and manually identified TGNs in terms of spatial overlap and visualization, while our proposed method has several advantages. First, our method performs automated TGN identification, and thus it provides an efficient tool to reduce expert labor costs and inter-operator bias relative to expert manual selection. Second, our method is robust to potential imaging artifacts and/or noise that can prevent successful manual ROI placement for TGN selection and hence yields a higher successful TGN identification rate.
Fan Zhang, Suheyla Cetin Karayumak, Nico Hoffmann, Yogesh Rathi, Alexandra J Golby, and Lauren J O'Donnell. 6/2020. “Deep White Matter Analysis (DeepWMA): Fast and Consistent Tractography Segmentation.” Med Image Anal, 65, Pp. 101761.Abstract
White matter tract segmentation, i.e. identifying tractography fibers (streamline trajectories) belonging to anatomically meaningful fiber tracts, is an essential step to enable tract quantification and visualization. In this study, we present a deep learning tractography segmentation method (DeepWMA) that allows fast and consistent identification of 54 major deep white matter fiber tracts from the whole brain. We create a large-scale training tractography dataset of 1 million labeled fiber samples, and we propose a novel 2D multi-channel feature descriptor (FiberMap) that encodes spatial coordinates of points along each fiber. We learn a convolutional neural network (CNN) fiber classification model based on FiberMap and obtain a high fiber classification accuracy of 90.99% on the training tractography data with ground truth fiber labels. Then, the method is evaluated on a test dataset of 597 diffusion MRI scans from six independently acquired populations across genders, the lifespan (1 day - 82 years), and different health conditions (healthy control, neuropsychiatric disorders, and brain tumor patients). We perform comparisons with two state-of-the-art tract segmentation methods. Experimental results show that our method obtains a highly consistent tract segmentation result, where on average over 99% of the fiber tracts are successfully identified across all subjects under study, most importantly, including neonates and patients with space-occupying brain tumors. We also demonstrate good generalization of the method to tractography data from multiple different fiber tracking methods. The proposed method leverages deep learning techniques and provides a fast and efficient tool for brain white matter segmentation in large diffusion MRI tractography datasets.
Shenyan Zong, Guofeng Shen, Chang-Sheng Mei, and Bruno Madore. 6/2020. “Improved PRF-Based MR Thermometry Using k-Space Energy Spectrum Analysis.” Magn Reson Med.Abstract
PURPOSE: Proton resonance frequency (PRF) thermometry encodes information in the phase of MRI signals. A multiplicative factor converts phase changes into temperature changes, and this factor includes the TE. However, phase variations caused by B and/or B inhomogeneities can effectively change TE in ways that vary from pixel to pixel. This work presents how spatial phase variations affect temperature maps and how to correct for corresponding errors. METHODS: A method called "k-space energy spectrum analysis" was used to map regions in the object domain to regions in the k-space domain. Focused ultrasound heating experiments were performed in tissue-mimicking gel phantoms under two scenarios: with and without proper shimming. The second scenario, with deliberately de-adjusted shimming, was meant to emulate B inhomogeneities in a controlled manner. The TE errors were mapped and compensated for using k-space energy spectrum analysis, and corrected results were compared with reference results. Furthermore, a volunteer was recruited to help evaluate the magnitude of the errors being corrected. RESULTS: The in vivo abdominal results showed that the TE and heating errors being corrected can readily exceed 10%. In phantom results, a linear regression between reference and corrected temperatures results provided a slope of 0.971 and R of 0.9964. Analysis based on the Bland-Altman method provided a bias of -0.0977°C and 95% limits of agreement that were 0.75°C apart. CONCLUSION: Spatially varying TE errors, such as caused by B and/or B inhomogeneities, can be detected and corrected using the k-space energy spectrum analysis method, for increased accuracy in proton resonance frequency thermometry.
Cheng-Chieh Cheng, Frank Preiswerk, and Bruno Madore. 6/2020. “Multi-pathway Multi-echo Acquisition and Neural Contrast Translation to Generate a Variety of Quantitative and Qualitative Image Contrasts.” Magn Reson Med, 83, 6, Pp. 2310-21.Abstract
PURPOSE: Clinical exams typically involve acquiring many different image contrasts to help discriminate healthy from diseased states. Ideally, 3D quantitative maps of all of the main MR parameters would be obtained for improved tissue characterization. Using data from a 7-min whole-brain multi-pathway multi-echo (MPME) scan, we aimed to synthesize several 3D quantitative maps (T and T ) and qualitative contrasts (MPRAGE, FLAIR, T -weighted, T -weighted, and proton density [PD]-weighted). The ability of MPME acquisitions to capture large amounts of information in a relatively short amount of time suggests it may help reduce the duration of neuro MR exams. METHODS: Eight healthy volunteers were imaged at 3.0T using a 3D isotropic (1.2 mm) MPME sequence. Spin-echo, MPRAGE, and FLAIR scans were performed for training and validation. MPME signals were interpreted through neural networks for predictions of different quantitative and qualitative contrasts. Predictions were compared to reference values at voxel and region-of-interest levels. RESULTS: Mean absolute errors (MAEs) for T and T maps were 216 ms and 11 ms, respectively. In ROIs containing white matter (WM) and thalamus tissues, the mean T /T predicted values were 899/62 ms and 1139/58 ms, consistent with reference values of 850/66 ms and 1126/58 ms, respectively. For qualitative contrasts, signals were normalized to those of WM, and MAEs for MPRAGE, FLAIR, T -weighted, T -weighted, and PD-weighted contrasts were 0.14, 0.15, 0.13, 0.16, and 0.05, respectively. CONCLUSIONS: Using an MPME sequence and neural-network contrast translation, whole-brain results were obtained with a variety of quantitative and qualitative contrast in ~6.8 min.
Naoyuki Shono, Brian Ninni, Franklin King, Takahisa Kato, Junichi Tokuda, Takahiro Fujimoto, Kemal Tuncali, and Nobuhiko Hata. 6/2020. “Simulated Accuracy Assessment of Small Footprint Body-mounted Probe Alignment Device for MRI-guided Cryotherapy of Abdominal Lesions.” Med Phys, 47, 6, Pp. 2337-49.Abstract
PURPOSE: Magnetic resonance imaging (MRI)-guided percutaneous cryotherapy of abdominal lesions, an established procedure, uses MRI to guide and monitor the cryoablation of lesions. Methods to precisely guide cryotherapy probes with a minimum amount of trial-and-error are yet to be established. To aid physicians in attaining precise probe alignment without trial-and-error, a body-mounted motorized cryotherapy-probe alignment device (BMCPAD) with motion compensation was clinically tested in this study. The study also compared the contribution of body motion and organ motion compensation to the guidance accuracy of a body-mounted probe alignment device. METHODS: The accuracy of guidance using the BMCPAD was prospectively measured during MRI-guided percutaneous cryotherapies before insertion of the probes. Clinical parameters including patient age, types of anesthesia, depths of the target, and organ sites of target were collected. By using MR images of the target organs and fiducial markers embedded in the BMCPAD, we retrospectively simulated the guidance accuracy with body motion compensation, organ motion compensation, and no compensation. The collected data were analyzed to test the impact of motion compensation on the guidance accuracy. RESULTS: Thirty-seven physical guidance of probes were prospectively recorded for sixteen completed cases. The accuracy of physical guidance using the BMCPAD was 13.4 ± 11.1 mm. The simulated accuracy of guidance with body motion compensation, organ motion compensation, and no compensation was 2.4 ± 2.9 mm, 2.2 ± 1.6 mm, and 3.5 ± 2.9 mm, respectively. Data analysis revealed that the body motion compensation and organ motion compensation individually impacted the improvement in the accuracy of simulated guidance. Moreover, the difference in the accuracy of guidance either by body motion compensation or organ motion compensation was not statistically significant. The major clinical parameters impacting the accuracy of guidance were the body and organ motions. Patient age, types of anesthesia, depths of the target, and organ sites of target did not influence the accuracy of guidance using BMCPAD. The magnitude of body surface movement and organ movement exhibited mutual statistical correlation. CONCLUSIONS: The BMCPAD demonstrated guidance accuracy comparable to that of previously reported devices for CT-guided procedures. The analysis using simulated motion compensation revealed that body motion compensation and organ motion compensation individually impact the improvement in the accuracy of device-guided cryotherapy probe alignment. Considering the correlation between body and organ movements, we also determined that body motion compensation using the ring fiducial markers in the BMCPAD can be solely used to address both body and organ motions in MRI-guided cryotherapy.
Saramati Narasimhan, Jared A Weis, Ma Luo, Amber L Simpson, Reid C Thompson, and Michael I Miga. 5/2020. “Accounting for Intraoperative Brain Shift Ascribable to Cavity Collapse During Intracranial Tumor Resection.” J Med Imaging (Bellingham), 7, 3, Pp. 031506.Abstract
For many patients with intracranial tumors, accurate surgical resection is a mainstay of their treatment paradigm. During surgical resection, image guidance is used to aid in localization and resection. Intraoperative brain shift can invalidate these guidance systems. One cause of intraoperative brain shift is cavity collapse due to tumor resection, which will be referred to as "debulking." We developed an imaging-driven finite element model of debulking to create a comprehensive simulation data set to reflect possible intraoperative changes. The objective was to create a method to account for brain shift due to debulking for applications in image-guided neurosurgery. We hypothesized that accounting for tumor debulking in a deformation atlas data framework would improve brain shift predictions, which would enhance image-based surgical guidance. This was evaluated in a six-patient intracranial tumor resection intraoperative data set. The brain shift deformation atlas data framework consisted of simulated deformations to account for effects due to gravity-induced and hyperosmotic drug-induced brain shift, which reflects previous developments. An additional complement of deformations involving simulated tumor growth followed by debulking was created to capture observed intraoperative effects not previously included. In five of six patient cases evaluated, inclusion of debulking mechanics improved brain shift correction by capturing global mass effects resulting from the resected tumor. These findings suggest imaging-driven brain shift models used to create a deformation simulation data framework of observed intraoperative events can be used to assist in more accurate image-guided surgical navigation in the brain.
Ron Kikinis and William M Wells. 5/2020. “Detection of Brain Metastases with Deep Learning Single-Shot Detector Algorithms.” Radiology, 295, 2, Pp. 416-7.
Junichi Tokuda, Qun Wang, Kemal Tuncali, Ravi T Seethamraju, Clare M Tempany, and Ehud J Schmidt. 5/2020. “Temperature-Sensitive Frozen-Tissue Imaging for Cryoablation Monitoring Using STIR-UTE MRI.” Invest Radiol, 55, 5, Pp. 310-7.Abstract
PURPOSE: The aim of this study was to develop a method to delineate the lethally frozen-tissue region (temperature less than -40°C) arising from interventional cryoablation procedures using a short tau inversion-recovery ultrashort echo-time (STIR-UTE) magnetic resonance (MR) imaging sequence. This method could serve as an intraprocedural validation of the completion of tumor ablation, reducing the number of local recurrences after cryoablation procedures. MATERIALS AND METHODS: The method relies on the short T1 and T2* relaxation times of frozen soft tissue. Pointwise Encoding Time with Radial Acquisition, a 3-dimensional UTE sequence with TE = 70 microseconds, was optimized with STIR to null tissues with a T1 of approximately 271 milliseconds, the threshold T1. Because the T1 relaxation time of frozen tissue in the temperature range of -40°C < temperature < -8°C is shorter than the threshold T1 at the 3-tesla magnetic field, tissues in this range should appear hyperintense. The sequence was evaluated in ex vivo frozen tissue, where image intensity and actual tissue temperatures, measured by thermocouples, were correlated. Thereafter, the sequence was evaluated clinically in 12 MR-guided prostate cancer cryoablations, where MR-compatible cryoprobes were used to destroy cancerous tissue and preserve surrounding normal tissue. RESULTS: The ex vivo experiment using a bovine muscle demonstrated that STIR-UTE images showed regions approximately between -40°C and -8°C as hyperintense, with tissues at lower and higher temperatures appearing dark, making it possible to identify the region likely to be above the lethal temperature inside the frozen tissue. In the clinical cases, the STIR-UTE images showed a dark volume centered on the cryoprobe shaft, Vinner, where the temperature is likely below -40°C, surrounded by a doughnut-shaped hyperintense volume, where the temperature is likely between -40°C and -8°C. The hyperintense region was itself surrounded by a dark volume, where the temperature is likely above -8°C, permitting calculation of Vouter. The STIR-UTE frozen-tissue volumes, Vinner and Vouter, appeared significantly smaller than signal voids on turbo spin echo images (P < 1.0 × 10), which are currently used to quantify the frozen-tissue volume ("the iceball"). The ratios of the Vinner and Vouter volumes to the iceball were 0.92 ± 0.08 and 0.29 ± 0.07, respectively. In a single postablation follow-up case, a strong correlation was seen between Vinner and the necrotic volume. CONCLUSIONS: Short tau inversion-recovery ultrashort echo-time MR imaging successfully delineated the area approximately between -40°C and -8°C isotherms in the frozen tissue, demonstrating its potential to monitor the lethal ablation volume during MR-guided cryoablation.
Shun Yao, Pan Lin, Matthew Vera, Farhana Akter, Ru-Yuan Zhang, Ailiang Zeng, Alexandra J Golby, Guozheng Xu, Yanmei Tie, and Jian Song. 4/2020. “Hormone Levels are Related to Functional Compensation in Prolactinomas: A Resting-state fMRI Study.” J Neurol Sci, 411, Pp. 116720.Abstract
Prolactinomas are tumors of the pituitary gland, which overproduces prolactin leading to dramatic fluctuations of endogenous hormone levels throughout the body. While it is not fully understood how endogenous hormone disorders affect a patient's brain, it is well known that fluctuating hormone levels can have negative neuropsychological effects. Using resting-state functional magnetic resonance imaging (rs-fMRI), we investigated whole-brain functional connectivity (FC) and its relationship with hormone levels in prolactinomas. By performing seed-based FC analyses, we compared FC metrics between 33 prolactinoma patients and 31 healthy controls matched for age, sex, and hand dominance. We then carried out a partial correlation analysis to examine the relationship between FC metrics and hormone levels. Compared to healthy controls, prolactinoma patients showed significantly increased thalamocortical and cerebellar-cerebral FC. Endogenous hormone levels were also positively correlated with increased FC metrics, and these hormone-FC relationships exhibited sex differences in prolactinoma patients. Our study is the first to reveal altered FC patterns in prolactinomas and to quantify the hormone-FC relationships. These results indicate the importance of endogenous hormones on functional compensation of the brain in patients with prolactinomas.
Lorenz Epprecht, Ahad Qureshi, Elliott D Kozin, Nicolas Vachicouras, Alexander M Huber, Ron Kikinis, Nikos Makris, Christian M Brown, Katherine L Reinshagen, and Daniel J Lee. 4/2020. “Human Cochlear Nucleus on 7 Tesla Diffusion Tensor Imaging: Insights Into Micro-anatomy and Function for Auditory Brainstem Implant Surgery.” Otol Neurotol, 41, 4, Pp. e484-e493.Abstract
OBJECTIVE: The cochlear nucleus (CN) is the target of the auditory brainstem implant (ABI). Most ABI candidates have Neurofibromatosis Type 2 (NF2) and distorted brainstem anatomy from bilateral vestibular schwannomas. The CN is difficult to characterize as routine structural MRI does not resolve detailed anatomy. We hypothesize that diffusion tensor imaging (DTI) enables both in vivo localization and quantitative measurements of CN morphology. STUDY DESIGN: We analyzed 7 Tesla (T) DTI images of 100 subjects (200 CN) and relevant anatomic structures using an MRI brainstem atlas with submillimetric (50 μm) resolution. SETTING: Tertiary referral center. PATIENTS: Young healthy normal hearing adults. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Diffusion scalar measures such as fractional anisotropy (FA), mean diffusivity (MD), mode of anisotropy (Mode), principal eigenvectors of the CN, and the adjacent inferior cerebellar peduncle (ICP). RESULTS: The CN had a lamellar structure and ventral-dorsal fiber orientation and could be localized lateral to the inferior cerebellar peduncle (ICP). This fiber orientation was orthogonal to tracts of the adjacent ICP where the fibers run mainly caudal-rostrally. The CN had lower FA compared to the medial aspect of the ICP (0.44 ± 0.09 vs. 0.64 ± 0.08, p < 0.001). CONCLUSIONS: 7T DTI enables characterization of human CN morphology and neuronal substructure. An ABI array insertion vector directed more caudally would better correspond to the main fiber axis of CN. State-of-the-art DTI has implications for ABI preoperative planning and future image guidance-assisted placement of the electrode array.
Rachel A Freedman, Rebecca S Gelman, Nathalie YR Agar, Sandro Santagata, Elizabeth C Randall, Begoña Gimenez-Cassina Lopez, Roisin M Connolly, Ian F Dunn, Catherine H Van Poznak, Carey K Anders, Michelle E Melisko, Kelly Silvestri, Christine M Cotter, Kathryn P Componeschi, Juan M Marte, Beverly Moy, Kimberly L Blackwell, Shannon L Puhalla, Nuhad Ibrahim, Timothy J Moynihan, Julie Nangia, Nadine Tung, Robyn Burns, Mothaffar F Rimawi, Ian E Krop, Antonio C Wolff, Eric P Winer, Nancy U Lin, and Nancy U Lin. 4/2020. “Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022.” Clin Breast Cancer, 20, 2, Pp. 145-51.Abstract
PURPOSE: This pilot study was performed to test our ability to administer neratinib monotherapy before clinically recommended craniotomy in patients with HER2-positive metastatic breast cancer to the central nervous system, to examine neratinib's central nervous system penetration at craniotomy, and to examine postoperative neratinib maintenance. PATIENTS AND METHODS: Patients with HER2-positive brain metastases undergoing clinically indicated cranial resection of a parenchymal tumor received neratinib 240 mg orally once a day for 7 to 21 days preoperatively, and resumed therapy postoperatively in 28-day cycles. Exploratory evaluations of time to disease progression, survival, and correlative tissue, cerebrospinal fluid (CSF), and blood-based analyses examining neratinib concentrations were planned. The study was registered at ClinicalTrials.gov under number NCT01494662. RESULTS: We enrolled 5 patients between May 22, 2013, and October 18, 2016. As of March 1, 2019, patients had remained on the study protocol for 1 to 75+ postoperative cycles pf therapy. Two patients had grade 3 diarrhea. Evaluation of the CSF showed low concentrations of neratinib; nonetheless, 2 patients continued to receive therapy without disease progression for at least 13 cycles, with one on-study treatment lasting for nearly 6 years. Neratinib distribution in surgical tissue was variable for 1 patient, while specimens from 2 others did not produce conclusive results as a result of limited available samples. CONCLUSION: Neratinib resulted in expected rates of diarrhea in this small cohort, with 2 of 5 patients receiving the study treatment for durable periods. Although logistically challenging, we were able to test a limited number of CSF- and parenchymal-based neratinib concentrations. Our findings from resected tumor tissue in one patient revealed heterogeneity in drug distribution and tumor histopathology.
Aida Steiner, Gabriela Alban, Teresa Cheng, Tina Kapur, Camden Bay, Pierre-Yves McLaughlin, Martin King, Clare Tempany, and Larissa J Lee. 4/2020. “Vaginal Recurrence of Endometrial Cancer: MRI Characteristics and Correlation With Patient Outcome After Salvage Radiation Therapy.” Abdom Radiol (NY), 45, 4, Pp. 1122-31.Abstract
PURPOSE: To evaluate MRI characteristics in vaginal recurrence of endometrial cancer (EC) including tumor volume shrinkage during salvage radiotherapy, and to identify imaging features associated with survival. METHODS: Patients with vaginal recurrence of EC treated with external beam radiotherapy (EBRT) followed by brachytherapy (BT), and with available pelvic MRI at two time points: baseline and/or before BT were retrospectively identified from 2004 to 2017. MRI features including recurrence location and tissue characteristics on T2- and T1-weighted images were evaluated at baseline only. Tumor volumes were measured both at baseline and pre-BT. Survival rates and associations were evaluated by Cox regression and Fisher's exact test, respectively. RESULTS: Sixty-two patients with 36 baseline and 50 pre-BT pelvic MRIs were included (24/62 with both MRIs). Vaginal recurrence of EC was most commonly located in the vaginal apex (27/36, 75%). Tumors with a post-contrast enhancing peripheral rim or low T2 signal rim at baseline showed longer recurrence-free survival (RFS) (HR 0.2, 95% CI 0.1-0.9, P < 0.05 adjusted for histology; HR 0.2, 95% CI 0.1-0.8, P < 0.05, respectively). The median tumor shrinkage at pre-BT was 69% (range 1-99%). Neither absolute tumor volumes nor volume regression at pre-BT were associated with RFS. Lymphovascular space invasion (LVSI) at hysterectomy and adjuvant RT were associated with recurrence involving the distal vagina (both P < 0.05). CONCLUSION: Vaginal recurrences with rim enhancement at baseline MRI predicted improved RFS, while tumor volume shrinkage at pre-BT did not. Distal vaginal recurrence was more common in patients with LVSI and adjuvant RT at EC diagnosis.
Lok Wa Laura Leung, Prashin Unadkat, Melina More Bertotti, Wenya Linda Bi, Walid Ibn Essayed, Adomas Bunevicius, Vamsidhar Chavakula, Laura Rigolo, Luca Fumagalli, Ziyun Tie, Alexandra J Golby, and Yanmei Tie. 3/2020. “Clinical Utility of Preoperative Bilingual Language fMRI Mapping in Patients with Brain Tumors.” J Neuroimaging, 30, 2, Pp. 175-83.Abstract
BACKGROUND AND PURPOSE: Previous literature has demonstrated disparity in the postoperative recovery of first and second language function of bilingual neurosurgical patients. However, it is unclear to whether preoperative brain mapping of both languages is needed. In this study, we aimed to evaluate the clinical utility of language task functional MRI (fMRI) implemented in both languages in bilingual patients. METHODS: We retrospectively examined fMRI data of 13 bilingual brain tumor patients (age: 23 to 59 years) who performed antonym generation task-based fMRIs in English and non-English language. The usefulness of bilingual language mapping was evaluated using a structured survey administered to 5 neurosurgeons. Additionally, quantitative comparison between the brain activation maps of both languages was performed. RESULTS: Survey responses revealed differences in raters' surgical approach, including asleep versus awake surgery and extent of resection, after viewing the language fMRI maps. Additional non-English fMRI led to changes in surgical decision-making and bettered localization of language areas. Quantitative analysis revealed an increase in laterality index (LI) in non-English fMRI compared to English fMRI. The Dice coefficient demonstrated fair overlap (.458 ± .160) between the activation maps. CONCLUSION: Bilingual fMRI mapping of bilingual patients allows to better appreciate functionally active language areas that may be neglected in single language mapping. Utility of bilingual mapping was supported by changes in both surgical approach and LI measurements, suggesting its benefit on preoperative language mapping.

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