Publications

2019
Cheng C-C, Preiswerk F, Hoge WS, Kuo T-H, Madore B. Multipathway Multi-echo (MPME) Imaging: All Main MR Parameters Mapped Based on a Single 3D Scan. Magn Reson Med. 2019;81 (3) :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.
deSouza NM, Tempany CM. A Risk-based Approach to Identifying Oligometastatic Disease on Imaging. Int J Cancer. 2019;144 (3) :422-30.Abstract
Recognition of <3 metastases in <2 organs, particularly in cancers with a known predisposition to oligometastatic disease (OMD) (colorectal, prostate, renal, sarcoma and lung), offers the opportunity to focally treat the lesions identified and confers a survival advantage. The reliability with which OMD is identified depends on the sensitivity of the imaging technique used for detection and may be predicted from phenotypic and genetic factors of the primary tumour, which determine metastatic risk. Whole-body or organ-specific imaging to identify oligometastases requires optimization to achieve maximal sensitivity. Metastatic lesions at multiple locations may require a variety of imaging modalities for best visualisation because the optimal image contrast is determined by tumour biology. Newer imaging techniques used for this purpose require validation. Additionally, rationalisation of imaging strategies is needed, particularly with regard to timing of imaging and follow-up studies. This article reviews the current evidence for the use of imaging for recognising OMD and proposes a risk-based roadmap for identifying patients with true OMD, or at risk of metastatic disease likely to be OM.
Alessandrino F, Taghipour M, Hassanzadeh E, Ziaei A, Vangel M, Fedorov A, Tempany CM, Fennessy FM. Predictive Role of PI-RADSv2 and ADC Parameters in Differentiating Gleason Pattern 3 + 4 and 4 + 3 Prostate Cancer. Abdom Radiol (NY). 2019;44 (1) :279-85.Abstract
PURPOSE: To compare the predictive roles of qualitative (PI-RADSv2) and quantitative assessment (ADC metrics), in differentiating Gleason pattern (GP) 3 + 4 from the more aggressive GP 4 + 3 prostate cancer (PCa) using radical prostatectomy (RP) specimen as the reference standard. METHODS: We retrospectively identified treatment-naïve peripheral (PZ) and transitional zone (TZ) Gleason Score 7 PCa patients who underwent multiparametric 3T prostate MRI (DWI with b value of 0,1400 and where unavailable, 0,500) and subsequent RP from 2011 to 2015. For each lesion identified on MRI, a PI-RADSv2 score was assigned by a radiologist blinded to pathology data. A PI-RADSv2 score ≤ 3 was defined as "low risk," a PI-RADSv2 score ≥ 4 as "high risk" for clinically significant PCa. Mean tumor ADC (ADC), ADC of adjacent normal tissue (ADC), and ADC (ADC/ADC) were calculated. Stepwise regression analysis using tumor location, ADC and ADC, b value, low vs. high PI-RADSv2 score was performed to differentiate GP 3 + 4 from 4 + 3. RESULTS: 119 out of 645 cases initially identified met eligibility requirements. 76 lesions were GP 3 + 4, 43 were 4 + 3. ADC was significantly different between the two GP groups (p = 0.001). PI-RADSv2 score ("low" vs. "high") was not significantly different between the two GP groups (p = 0.17). Regression analysis selected ADC (p = 0.03) and ADC (p = 0.0007) as best predictors to differentiate GP 4 + 3 from 3 + 4. Estimated sensitivity, specificity, and accuracy of the predictive model in differentiating GP 4 + 3 from 3 + 4 were 37, 82, and 66%, respectively. CONCLUSIONS: ADC metrics could differentiate GP 3 + 4 from 4 + 3 PCa with high specificity and moderate accuracy while PI-RADSv2, did not differentiate between these patterns.
O'Donnell LJ, Daducci A, Wassermann D, Lenglet C. Advances in Computational and Statistical Diffusion MRI. NMR Biomed. 2019;32 (4) :e3805.Abstract
Computational methods are crucial for the analysis of diffusion magnetic resonance imaging (MRI) of the brain. Computational diffusion MRI can provide rich information at many size scales, including local microstructure measures such as diffusion anisotropies or apparent axon diameters, whole-brain connectivity information that describes the brain's wiring diagram and population-based studies in health and disease. Many of the diffusion MRI analyses performed today were not possible five, ten or twenty years ago, due to the requirements for large amounts of computer memory or processor time. In addition, mathematical frameworks had to be developed or adapted from other fields to create new ways to analyze diffusion MRI data. The purpose of this review is to highlight recent computational and statistical advances in diffusion MRI and to put these advances into context by comparison with the more traditional computational methods that are in popular clinical and scientific use. We aim to provide a high-level overview of interest to diffusion MRI researchers, with a more in-depth treatment to illustrate selected computational advances.
2018
Arai S, Jonas O, Whitman MA, Corey E, Balk SP, Chen S. Tyrosine Kinase Inhibitors Increase MCL1 Degradation and in Combination with BCLXL/BCL2 Inhibitors Drive Prostate Cancer Apoptosis. Clin Cancer Res. 2018;24 (21) :5458-5470.Abstract
Clinically available BH3 mimetic drugs targeting BCLXL and/or BCL2 (navitoclax and venetoclax, respectively) are effective in some hematologic malignancies, but have limited efficacy in solid tumors. This study aimed to identify combination therapies that exploit clinical BH3 mimetics for prostate cancer. Prostate cancer cells or xenografts were treated with BH3 mimetics as single agents or in combination with other agents, and effects on MCL1 and apoptosis were assessed. MCL1 was also targeted directly using RNAi, CRISPR, or an MCL1-specific BH3 mimetic, S63845. We initially found that MCL1 depletion or inhibition markedly sensitized prostate cancer cells to apoptosis mediated by navitoclax, but not venetoclax, and , indicating that they are primed to undergo apoptosis and protected by MCL1 and BCLXL. Small-molecule EGFR kinase inhibitors (erlotinib, lapatinib) also dramatically sensitized to navitoclax-mediated apoptosis, and this was associated with markedly increased proteasome-dependent degradation of MCL1. This increased MCL1 degradation appeared to be through a novel mechanism, as it was not dependent upon GSK3β-mediated phosphorylation and subsequent ubiquitylation by the ubiquitin ligases βTRCP and FBW7, or through other previously identified MCL1 ubiquitin ligases or deubiquitinases. Inhibitors targeting additional kinases (cabozantinib and sorafenib) similarly caused GSK3β-independent MCL1 degradation, and in combination with navitoclax drove apoptosis and These results show that prostate cancer cells are primed to undergo apoptosis and that cotargeting BCLXL and MCL1, directly or indirectly through agents that increase MCL1 degradation, can induce dramatic apoptotic responses. .
Wu Y, Zhang F, Makris N, Ning Y, Norton I, She S, Peng H, Rathi Y, Feng Y, Wu H, et al. Investigation into Local White Matter Abnormality in Emotional Processing and Sensorimotor Areas using an Automatically Annotated Fiber Clustering in Major Depressive Disorder. Neuroimage. 2018;181 :16-29.Abstract
This work presents an automatically annotated fiber cluster (AAFC) method to enable identification of anatomically meaningful white matter structures from the whole brain tractography. The proposed method consists of 1) a study-specific whole brain white matter parcellation using a well-established data-driven groupwise fiber clustering pipeline to segment tractography into multiple fiber clusters, and 2) a novel cluster annotation method to automatically assign an anatomical tract annotation to each fiber cluster by employing cortical parcellation information across multiple subjects. The novelty of the AAFC method is that it leverages group-wise information about the fiber clusters, including their fiber geometry and cortical terminations, to compute a tract anatomical label for each cluster in an automated fashion. We demonstrate the proposed AAFC method in an application of investigating white matter abnormality in emotional processing and sensorimotor areas in major depressive disorder (MDD). Seven tracts of interest related to emotional processing and sensorimotor functions are automatically identified using the proposed AAFC method as well as a comparable method that uses a cortical parcellation alone. Experimental results indicate that our proposed method is more consistent in identifying the tracts across subjects and across hemispheres in terms of the number of fibers. In addition, we perform a between-group statistical analysis in 31 MDD patients and 62 healthy subjects on the identified tracts using our AAFC method. We find statistical differences in diffusion measures in local regions within a fiber tract (e.g. 4 fiber clusters within the identified left hemisphere cingulum bundle (consisting of 14 clusters) are significantly different between the two groups), suggesting the ability of our method in identifying potential abnormality specific to subdivisions of a white matter structure.
Herrmann MD, Clunie DA, Fedorov A, Doyle SW, Pieper S, Klepeis V, Le LP, Mutter GL, Milstone DS, Schultz TJ, et al. Implementing the DICOM Standard for Digital Pathology. J Pathol Inform. 2018;9 :37.Abstract
Background: Digital Imaging and Communications in Medicine (DICOM) is the standard for the representation, storage, and communication of medical images and related information. A DICOM file format and communication protocol for pathology have been defined; however, adoption by vendors and in the field is pending. Here, we implemented the essential aspects of the standard and assessed its capabilities and limitations in a multisite, multivendor healthcare network. Methods: We selected relevant DICOM attributes, developed a program that extracts pixel data and pixel-related metadata, integrated patient and specimen-related metadata, populated and encoded DICOM attributes, and stored DICOM files. We generated the files using image data from four vendor-specific image file formats and clinical metadata from two departments with different laboratory information systems. We validated the generated DICOM files using recognized DICOM validation tools and measured encoding, storage, and access efficiency for three image compression methods. Finally, we evaluated storing, querying, and retrieving data over the web using existing DICOM archive software. Results: Whole slide image data can be encoded together with relevant patient and specimen-related metadata as DICOM objects. These objects can be accessed efficiently from files or through RESTful web services using existing software implementations. Performance measurements show that the choice of image compression method has a major impact on data access efficiency. For lossy compression, JPEG achieves the fastest compression/decompression rates. For lossless compression, JPEG-LS significantly outperforms JPEG 2000 with respect to data encoding and decoding speed. Conclusion: Implementation of DICOM allows efficient access to image data as well as associated metadata. By leveraging a wealth of existing infrastructure solutions, the use of DICOM facilitates enterprise integration and data exchange for digital pathology.
Fedorov A, Schwier M, Clunie D, Herz C, Pieper S, Kikinis R, Tempany C, Fennessy F. An Annotated Test-retest Collection of Prostate Multiparametric MRI. Sci Data. 2018;5 :180281.Abstract
Multiparametric Magnetic Resonance Imaging (mpMRI) is widely used for characterizing prostate cancer. Standard of care use of mpMRI in clinic relies on visual interpretation of the images by an expert. mpMRI is also increasingly used as a quantitative imaging biomarker of the disease. Little is known about repeatability of such quantitative measurements, and no test-retest datasets have been available publicly to support investigation of the technical characteristics of the MRI-based quantification in the prostate. Here we present an mpMRI dataset consisting of baseline and repeat prostate MRI exams for 15 subjects, manually annotated to define regions corresponding to lesions and anatomical structures, and accompanied by region-based measurements. This dataset aims to support further investigation of the repeatability of mpMRI-derived quantitative prostate measurements, study of the robustness and reliability of the automated analysis approaches, and to support development and validation of new image analysis techniques. The manuscript can also serve as an example of the use of DICOM for standardized encoding of the image annotation and quantification results.
Randall EC, Emdal KB, Laramy JK, Kim M, Roos A, Calligaris D, Regan MS, Gupta SK, Mladek AC, Carlson BL, et al. Integrated Mapping of Pharmacokinetics and Pharmacodynamics in a Patient-derived Xenograft Model of Glioblastoma. Nat Commun. 2018;9 (1) :4904.Abstract
Therapeutic options for the treatment of glioblastoma remain inadequate despite concerted research efforts in drug development. Therapeutic failure can result from poor permeability of the blood-brain barrier, heterogeneous drug distribution, and development of resistance. Elucidation of relationships among such parameters could enable the development of predictive models of drug response in patients and inform drug development. Complementary analyses were applied to a glioblastoma patient-derived xenograft model in order to quantitatively map distribution and resulting cellular response to the EGFR inhibitor erlotinib. Mass spectrometry images of erlotinib were registered to histology and magnetic resonance images in order to correlate drug distribution with tumor characteristics. Phosphoproteomics and immunohistochemistry were used to assess protein signaling in response to drug, and integrated with transcriptional response using mRNA sequencing. This comprehensive dataset provides simultaneous insight into pharmacokinetics and pharmacodynamics and indicates that erlotinib delivery to intracranial tumors is insufficient to inhibit EGFR tyrosine kinase signaling.
Peled S, Vangel M, Kikinis R, Tempany CM, Fennessy FM, Fedorov A. Selection of Fitting Model and Arterial Input Function for Repeatability in Dynamic Contrast-Enhanced Prostate MRI. Acad Radiol. 2018.Abstract
RATIONALE AND OBJECTIVES: Analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging is notable for the variability of calculated parameters. The purpose of this study was to evaluate the level of measurement variability and error/variability due to modeling in DCE magnetic resonance imaging parameters. MATERIALS AND METHODS: Two prostate DCE scans were performed on 11 treatment-naïve patients with suspected or confirmed prostate peripheral zone cancer within an interval of less than two weeks. Tumor-suspicious and normal-appearing regions of interest (ROI) in the prostate peripheral zone were segmented. Different Tofts-Kety based models and different arterial input functions, with and without bolus arrival time (BAT) correction, were used to extract pharmacokinetic parameters. The percent repeatability coefficient (%RC) of fitted model parameters K, v, and k was calculated. Paired t-tests comparing parameters in tumor-suspicious ROIs and in normal-appearing tissue evaluated each parameter's sensitivity to pathology. RESULTS: Although goodness-of-fit criteria favored the four-parameter extended Tofts-Kety model with the BAT correction included, the simplest two-parameter Tofts-Kety model overall yielded the best repeatability scores. The best %RC in the tumor-suspicious ROI was 63% for k, 28% for v and 83% for K . The best p values for discrimination between tissues were p <10 for k and K, and p = 0.11 for v. Addition of the BAT correction to the models did not improve repeatability. CONCLUSION: The parameter k, using an arterial input functions directly measured from blood signals, was more repeatable than K. Both K and k values were highly discriminatory between healthy and diseased tissues in all cases. The parameter v had high repeatability but could not distinguish the two tissue types.
Moreira P, Patel N, Wartenberg M, Li G, Tuncali K, Heffter T, Burdette EC, Iordachita I, Fischer GS, Hata N, et al. Evaluation of Robot-assisted MRI-guided Prostate Biopsy: Needle Path Analysis during Clinical Trials. Phys Med Biol. 2018;63 (20) :20NT02.Abstract
PURPOSE: While the interaction between a needle and the surrounding tissue is known to cause a significant targeting error in prostate biopsy leading to false-negative results, few studies have demonstrated how it impacts in the actual procedure. We performed a pilot study on robot-assisted MRI-guided prostate biopsy with an emphasis on the in-depth analysis of the needle-tissue interaction in-vivo. Methods: The data were acquired during in-bore transperineal prostate biopsies in patients using a 4 degrees-of-freedom (DoF) MRI-compatible robot. The anatomical structures in the pelvic area and the needle path were reconstructed from MR images, and quantitatively analyzed. We analyzed each structure individually and also proposed a mathematical model to investigate the influence of those structures in the targeting error using the mixed-model regression. Results: The median targeting error in 188 insertions (27 patients) was 6.3mm. Both the individual anatomical structure analysis and the mixed-model analysis showed that the deviation resulted from the contact between the needle and the skin as the main source of error. On contrary, needle bending inside the tissue (expressed as needle curvature) did not vary among insertions with targeting errors above and below the average. The analysis indicated that insertions crossing the bulbospongiosus presented a targeting error lower than the average. The mixed-model analysis demonstrated that the distance between the needle guide and the patient skin, the deviation at the entry point, and the path length inside the pelvic diaphragm had a statistically significant contribution to the targeting error (p<0.05). Conclusions: Our results indicate that the errors associated with the elastic contact between the needle and the skin were more prominent than the needle bending along the insertion. Our findings will help to improve the preoperative planning of transperineal prostate biopsies.
Lasso A, Nam HH, Dinh PV, Pinter C, Fillion-Robin J-C, Pieper S, Jhaveri S, Vimort J-B, Martin K, Asselin M, et al. Interaction with Volume-Rendered Three-Dimensional Echocardiographic Images in Virtual Reality. J Am Soc Echocardiogr. 2018;31 (10) :1158-60.
Basu SS, Randall EC, Regan MS, Lopez BGC, Clark AR, Schmitt ND, Agar JN, Dillon DA, Agar NYR. In Vitro Liquid Extraction Surface Analysis Mass Spectrometry (ivLESA-MS) for Direct Metabolic Analysis of Adherent Cells in Culture. Anal Chem. 2018;90 (8) :4987-91.Abstract
Conventional metabolomic methods include extensive sample preparation steps and long analytical run times, increasing the likelihood of processing artifacts and limiting high throughput applications. We present here in vitro liquid extraction surface analysis mass spectrometry (ivLESA-MS), a variation on LESA-MS, performed directly on adherent cells grown in 96-well cell culture plates. To accomplish this, culture medium was aspirated immediately prior to analysis, and metabolites were extracted using LESA from the cell monolayer surface, followed by nano-electrospray ionization and MS analysis in negative ion mode. We applied this platform to characterize and compare lipidomic profiles of multiple breast cancer cell lines growing in culture (MCF-7, ZR-75-1, MDA-MB-453, and MDA-MB-231) and revealed distinct and reproducible lipidomic signatures between the cell lines. Additionally, we demonstrated time-dependent processing artifacts, underscoring the importance of immediate analysis. ivLESA-MS represents a rapid in vitro metabolomic method, which precludes the need for quenching, cell harvesting, sample preparation, and chromatography, significantly shortening preparation and analysis time while minimizing processing artifacts. This method could be further adapted to test drugs in vitro in a high throughput manner.
van Beek EJR, Kuhl C, Anzai Y, Desmond P, Ehman RL, Gong Q, Gold G, Gulani V, Hall-Craggs M, Leiner T, et al. Value of MRI in Medicine: More Than Just Another Test?. J Magn Reson Imaging. 2018.Abstract
There is increasing scrutiny from healthcare organizations towards the utility and associated costs of imaging. MRI has traditionally been used as a high-end modality, and although shown extremely important for many types of clinical scenarios, it has been suggested as too expensive by some. This editorial will try and explain how value should be addressed and gives some insights and practical examples of how value of MRI can be increased. It requires a global effort to increase accessibility, value for money, and impact on patient management. We hope this editorial sheds some light and gives some indications of where the field may wish to address some of its research to proactively demonstrate the value of MRI. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.
Beek JMRI 2018
Guenette JP, Seethamraju RT, Jayender J, Corrales CE, Lee TC. MR Imaging of the Facial Nerve through the Temporal Bone at 3T with a Noncontrast Ultrashort Echo Time Sequence. AJNR Am J Neuroradiol. 2018;39 (10) :1903-6.Abstract
The pointwise encoding time reduction with radial acquisition (PETRA) ultrashort echo time MR imaging sequence at 3T enables visualization of the facial nerve from the brain stem, through the temporal bone, to the stylomastoid foramen without intravenous contrast. Use of the PETRA sequence, or other ultrashort echo time sequences, should be considered in the MR imaging evaluation of certain skull base tumors and perhaps other facial nerve and temporal bone pathologies.
Luo J, Frisken S, Machado I, Zhang M, Pieper S, Golland P, Toews M, Unadkat P, Sedghi A, Zhou H, et al. Using the Variogram for Vector Outlier Screening: Application to Feature-based Image Registration. Int J Comput Assist Radiol Surg. 2018;13 (12) :1871-80.Abstract
PURPOSE: Matching points that are derived from features or landmarks in image data is a key step in some medical imaging applications. Since most robust point matching algorithms claim to be able to deal with outliers, users may place high confidence in the matching result and use it without further examination. However, for tasks such as feature-based registration in image-guided neurosurgery, even a few mismatches, in the form of invalid displacement vectors, could cause serious consequences. As a result, having an effective tool by which operators can manually screen all matches for outliers could substantially benefit the outcome of those applications. METHODS: We introduce a novel variogram-based outlier screening method for vectors. The variogram is a powerful geostatistical tool for characterizing the spatial dependence of stochastic processes. Since the spatial correlation of invalid displacement vectors, which are considered as vector outliers, tends to behave differently than normal displacement vectors, they can be efficiently identified on the variogram. RESULTS: We validate the proposed method on 9 sets of clinically acquired ultrasound data. In the experiment, potential outliers are flagged on the variogram by one operator and further evaluated by 8 experienced medical imaging researchers. The matching quality of those potential outliers is approximately 1.5 lower, on a scale from 1 (bad) to 5 (good), than valid displacement vectors. CONCLUSION: The variogram is a simple yet informative tool. While being used extensively in geostatistical analysis, it has not received enough attention in the medical imaging field. We believe there is a good deal of potential for clinically applying the proposed outlier screening method. By way of this paper, we also expect researchers to find variogram useful in other medical applications that involve motion vectors analyses.
Zhang F, Wu Y, Norton I, Rigolo L, Rathi Y, Makris N, O'Donnell LJ. An Anatomically Curated Fiber Clustering White Matter Atlas for Consistent White Matter Tract Parcellation across the Lifespan. Neuroimage. 2018;179 :429-47.Abstract
This work presents an anatomically curated white matter atlas to enable consistent white matter tract parcellation across different populations. Leveraging a well-established computational pipeline for fiber clustering, we create a tract-based white matter atlas including information from 100 subjects. A novel anatomical annotation method is proposed that leverages population-based brain anatomical information and expert neuroanatomical knowledge to annotate and categorize the fiber clusters. A total of 256 white matter structures are annotated in the proposed atlas, which provides one of the most comprehensive tract-based white matter atlases covering the entire brain to date. These structures are composed of 58 deep white matter tracts including major long range association and projection tracts, commissural tracts, and tracts related to the brainstem and cerebellar connections, plus 198 short and medium range superficial fiber clusters organized into 16 categories according to the brain lobes they connect. Potential false positive connections are annotated in the atlas to enable their exclusion from analysis or visualization. In addition, the proposed atlas allows for a whole brain white matter parcellation into 800 fiber clusters to enable whole brain connectivity analyses. The atlas and related computational tools are open-source and publicly available. We evaluate the proposed atlas using a testing dataset of 584 diffusion MRI scans from multiple independently acquired populations, across genders, the lifespan (1 day-82 years), and different health conditions (healthy control, neuropsychiatric disorders, and brain tumor patients). Experimental results show successful white matter parcellation across subjects from different populations acquired on multiple scanners, irrespective of age, gender or disease indications. Over 99% of the fiber tracts annotated in the atlas were detected in all subjects on average. One advantage in terms of robustness is that the tract-based pipeline does not require any cortical or subcortical segmentations, which can have limited success in young children and patients with brain tumors or other structural lesions. We believe this is the first demonstration of consistent automated white matter tract parcellation across the full lifespan from birth to advanced age.
King MT, Nguyen PL, Boldbaatar N, Tempany CM, Cormack RA, Beard CJ, Hurwitz MD, Suh WW, D'Amico AV, Orio PF. Long-Term Outcomes of Partial Prostate Treatment with Magnetic Resonance Imaging-Guided Brachytherapy for Patients with Favorable-Risk Prostate Cancer. Cancer. 2018;124 (17) :3528-35.Abstract
BACKGROUND: Partial prostate treatment has emerged as a potential method for treating patients with favorable-risk prostate cancer while minimizing toxicity. The authors previously demonstrated poor rates of biochemical disease control for patients with National Comprehensive Cancer Network (NCCN) intermediate-risk disease using partial gland treatment with brachytherapy. The objective of the current study was to estimate the rates of distant metastasis and prostate cancer-specific mortality (PCSM) for this cohort. METHODS: Between 1997 and 2007, a total of 354 men with clinical T1c disease, a prostate-specific antigen (PSA) level < 15 ng/mL, and Gleason grade ≤3 + 4 prostate cancer underwent partial prostate treatment with brachytherapy to the peripheral zone under 0.5-Tesla magnetic resonance guidance. The cumulative incidences of metastasis and PCSM for the NCCN very low-risk, low-risk, and intermediate-risk groups were estimated. Fine and Gray competing risk regression was used to evaluate clinical factors associated with time to metastasis. RESULTS: A total of 22 patients developed metastases at a median of 11.0 years (interquartile range, 6.9-13.9 years). The 12-year metastasis rates for patients with very low-risk, low-risk, and intermediate-risk disease were 0.8% (95% confidence interval [95% CI], 0.1%-4.4%), 8.7% (95% CI, 3.4%-17.2%), and 15.7% (95% CI, 5.7%-30.2%), respectively, and the 12-year PCSM estimates were 1.6% (95% CI, 0.1%-7.6%), 1.4% (95% CI, 0.1%-6.8%), and 8.2% (95% CI, 1.9%-20.7%), respectively. On multivariate analysis, NCCN risk category (low risk: hazard ratio, 6.34 [95% CI, 1.18-34.06; P = .03] and intermediate risk: hazard ratio, 6.98 [95% CI, 1.23-39.73; P = .03]) was found to be significantly associated with the time to metastasis. CONCLUSIONS: Partial prostate treatment with brachytherapy may be associated with higher rates of distant metastasis and PCSM for patients with intermediate-risk disease after long-term follow-up. Treatment of less than the full gland may not be appropriate for this cohort. Cancer 2018. © 2018 American Cancer Society.
Wachinger C, Toews M, Langs G, Wells W, Golland P. Keypoint Transfer for Fast Whole-Body Segmentation. IEEE Trans Med Imaging. 2018.Abstract
We introduce an approach for image segmentation based on sparse correspondences between keypoints in testing and training images. Keypoints represent automatically identified distinctive image locations, where each keypoint correspondence suggests a transformation between images. We use these correspondences to transfer label maps of entire organs from the training images to the test image. The keypoint transfer algorithm includes three steps: (i) keypoint matching, (ii) voting-based keypoint labeling, and (iii) keypoint-based probabilistic transfer of organ segmentations. We report segmentation results for abdominal organs in whole-body CT and MRI, as well as in contrast-enhanced CT and MRI. Our method offers a speed-up of about three orders of magnitude in comparison to common multi-atlas segmentation, while achieving an accuracy that compares favorably. Moreover, keypoint transfer does not require the registration to an atlas or a training phase. Finally, the method allows for the segmentation of scans with highly variable field-of-view.
Hong Y, O'Donnell LJ, Savadjiev P, Zhang F, Wassermann D, Pasternak O, Johnson H, Paulsen J, Vonsattel J-P, Makris N, et al. Genetic Load Determines Atrophy in Hand Cortico-striatal Pathways in Presymptomatic Huntington's Disease. Hum Brain Mapp. 2018;39 (10) :3871-83.Abstract
Huntington's disease (HD) is an inherited neurodegenerative disorder that causes progressive breakdown of striatal neurons. Standard white matter integrity measures like fractional anisotropy and mean diffusivity derived from diffusion tensor imaging were analyzed in prodromal-HD subjects; however, they studied either a whole brain or specific subcortical white matter structures with connections to cortical motor areas. In this work, we propose a novel analysis of a longitudinal cohort of 243 prodromal-HD individuals and 88 healthy controls who underwent two or more diffusion MRI scans as part of the PREDICT-HD study. We separately trace specific white matter fiber tracts connecting the striatum (caudate and putamen) with four cortical regions corresponding to the hand, face, trunk, and leg motor areas. A multi-tensor tractography algorithm with an isotropic volume fraction compartment allows estimating diffusion of fast-moving extra-cellular water in regions containing crossing fibers and provides quantification of a microstructural property related to tissue atrophy. The tissue atrophy rate is separately analyzed in eight cortico-striatal pathways as a function of CAG-repeats (genetic load) by statistically regressing out age effect from our cohort. The results demonstrate a statistically significant increase in isotropic volume fraction (atrophy) bilaterally in hand fiber connections to the putamen with increasing CAG-repeats, which connects the genetic abnormality (CAG-repeats) to an imaging-based microstructural marker of tissue integrity in specific white matter pathways in HD. Isotropic volume fraction measures in eight cortico-striatal pathways are also correlated significantly with total motor scores and diagnostic confidence levels, providing evidence of their relevance to HD clinical presentation.

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