Publications

2018
Sanjay S Yengul, Paul E Barbone, and Bruno Madore. 2018. “Application of a Forward Model of Axisymmetric Shear Wave Propagation in Viscoelastic Media to Shear Wave Elastography.” J Acoust Soc Am, 143, 6, Pp. 3266.Abstract
A simple but general solution of Navier's equation for axisymmetric shear wave propagation in a homogeneous isotropic viscoelastic medium is presented. It is well-suited for use as a forward model for some acoustic radiation force impulse based shear wave elastography applications because it does not require precise knowledge of the strength of the source, nor its spatial or temporal distribution. Instead, it depends on two assumptions: (1) the source distribution is axisymmetric and confined to a small region near the axis of symmetry, and (2) the propagation medium is isotropic and homogeneous. The model accounts for the vector polarization of shear waves and exactly represents geometric spreading of the shear wavefield, whether spherical, cylindrical, or neither. It makes no assumption about the frequency dependence of material parameters, i.e., it is material-model independent. Validation using measured shear wavefields excited by acoustic radiation force in a homogeneous gelatin sample show that the model accounts for well over 90% of the measured wavefield "energy." An optimal fit of the model to simulated shear wavefields with noise in a homogeneous viscoelastic medium enables estimation of both the shear storage modulus and shear wave attenuation to within 1%.
David Black, Michael Unger, Nele Fischer, Ron Kikinis, Horst Hahn, Thomas Neumuth, and Bernhard Glaser. 2018. “Auditory Display as Feedback for a Novel Eye-tracking System for Sterile Operating Room Interaction.” Int J Comput Assist Radiol Surg, 13, 1, Pp. 37-45.Abstract
PURPOSE: The growing number of technical systems in the operating room has increased attention on developing touchless interaction methods for sterile conditions. However, touchless interaction paradigms lack the tactile feedback found in common input devices such as mice and keyboards. We propose a novel touchless eye-tracking interaction system with auditory display as a feedback method for completing typical operating room tasks. Auditory display provides feedback concerning the selected input into the eye-tracking system as well as a confirmation of the system response. METHODS: An eye-tracking system with a novel auditory display using both earcons and parameter-mapping sonification was developed to allow touchless interaction for six typical scrub nurse tasks. An evaluation with novice participants compared auditory display with visual display with respect to reaction time and a series of subjective measures. RESULTS: When using auditory display to substitute for the lost tactile feedback during eye-tracking interaction, participants exhibit reduced reaction time compared to using visual-only display. In addition, the auditory feedback led to lower subjective workload and higher usefulness and system acceptance ratings. CONCLUSION: Due to the absence of tactile feedback for eye-tracking and other touchless interaction methods, auditory display is shown to be a useful and necessary addition to new interaction concepts for the sterile operating room, reducing reaction times while improving subjective measures, including usefulness, user satisfaction, and cognitive workload.
David Black, Horst K Hahn, Ron Kikinis, Karin Wårdell, and Neda Haj-Hosseini. 2018. “Auditory Display for Fluorescence-guided Open Brain Tumor Surgery.” Int J Comput Assist Radiol Surg, 13, 1, Pp. 25-35.Abstract
PURPOSE: Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed and evaluated for communicating measured fluorescence intensity values directly to the surgeon. METHODS: The auditory display was programmed to map the values measured by the HHF probe to the playback of tones that represented three fluorescence intensity ranges and one error signal. Ten persons with no previous knowledge of the application took part in a laboratory evaluation. After a brief training period, participants performed measurements on a tray of 96 wells of liquid fluorescence phantom and verbally stated the perceived measurement values for each well. The latency and accuracy of the participants' verbal responses were recorded. The long-term memorization of sound function was evaluated in a second set of 10 participants 2-3 and 7-12 days after training. RESULTS: The participants identified the played tone accurately for 98% of measurements after training. The median response time to verbally identify the played tones was 2 pulses. No correlation was found between the latency and accuracy of the responses, and no significant correlation with the musical proficiency of the participants was observed on the function responses. Responses for the memory test were 100% accurate. CONCLUSION: The employed auditory display was shown to be intuitive, easy to learn and remember, fast to recognize, and accurate in providing users with measurements of fluorescence intensity or error signal. The results of this work establish a basis for implementing and further evaluating auditory displays in clinical scenarios involving fluorescence guidance and other areas for which categorized auditory display could be useful.
Jens Sjölund, Anders Eklund, Evren Özarslan, Magnus Herberthson, Maria Bånkestad, and Hans Knutsson. 2018. “Bayesian Uncertainty Quantification in Linear Models for Diffusion MRI.” Neuroimage, 175, Pp. 272-85.Abstract
Diffusion MRI (dMRI) is a valuable tool in the assessment of tissue microstructure. By fitting a model to the dMRI signal it is possible to derive various quantitative features. Several of the most popular dMRI signal models are expansions in an appropriately chosen basis, where the coefficients are determined using some variation of least-squares. However, such approaches lack any notion of uncertainty, which could be valuable in e.g. group analyses. In this work, we use a probabilistic interpretation of linear least-squares methods to recast popular dMRI models as Bayesian ones. This makes it possible to quantify the uncertainty of any derived quantity. In particular, for quantities that are affine functions of the coefficients, the posterior distribution can be expressed in closed-form. We simulated measurements from single- and double-tensor models where the correct values of several quantities are known, to validate that the theoretically derived quantiles agree with those observed empirically. We included results from residual bootstrap for comparison and found good agreement. The validation employed several different models: Diffusion Tensor Imaging (DTI), Mean Apparent Propagator MRI (MAP-MRI) and Constrained Spherical Deconvolution (CSD). We also used in vivo data to visualize maps of quantitative features and corresponding uncertainties, and to show how our approach can be used in a group analysis to downweight subjects with high uncertainty. In summary, we convert successful linear models for dMRI signal estimation to probabilistic models, capable of accurate uncertainty quantification.
Tony W Trinh, Daniel I Glazer, Cheryl A Sadow, Anik V Sahni, Nina L Geller, and Stuart G Silverman. 2018. “Bladder Cancer Diagnosis with CT Urography: Test Characteristics and Reasons for False-positive and False-negative Results.” Abdom Radiol (NY), 43, 3, Pp. 663-71.Abstract
PURPOSE: To determine test characteristics of CT urography for detecting bladder cancer in patients with hematuria and those undergoing surveillance, and to analyze reasons for false-positive and false-negative results. METHODS: A HIPAA-compliant, IRB-approved retrospective review of reports from 1623 CT urograms between 10/2010 and 12/31/2013 was performed. 710 examinations for hematuria or bladder cancer history were compared to cystoscopy performed within 6 months. Reference standard was surgical pathology or 1-year minimum clinical follow-up. False-positive and false-negative examinations were reviewed to determine reasons for errors. RESULTS: Ninety-five bladder cancers were detected. CT urography accuracy: was 91.5% (650/710), sensitivity 86.3% (82/95), specificity 92.4% (568/615), positive predictive value 63.6% (82/129), and negative predictive value was 97.8% (568/581). Of 43 false positives, the majority of interpretation errors were due to benign prostatic hyperplasia (n = 12), trabeculated bladder (n = 9), and treatment changes (n = 8). Other causes include blood clots, mistaken normal anatomy, infectious/inflammatory changes, or had no cystoscopic correlate. Of 13 false negatives, 11 were due to technique, one to a large urinary residual, one to artifact. There were no errors in perception. CONCLUSION: CT urography is an accurate test for diagnosing bladder cancer; however, in protocols relying predominantly on excretory phase images, overall sensitivity remains insufficient to obviate cystoscopy. Awareness of bladder cancer mimics may reduce false-positive results. Improvements in CTU technique may reduce false-negative results.
Laura Stefanik, Lauren Erdman, Stephanie H Ameis, George Foussias, Benoit H Mulsant, Tina Behdinan, Anna Goldenberg, Lauren J O'Donnell, and Aristotle N Voineskos. 2018. “Brain-Behavior Participant Similarity Networks Among Youth and Emerging Adults with Schizophrenia Spectrum, Autism Spectrum, or Bipolar Disorder and Matched Controls.” Neuropsychopharmacology, 43, 5, Pp. 1180-8.Abstract
There is considerable heterogeneity in social cognitive and neurocognitive performance among people with schizophrenia spectrum disorders (SSD), autism spectrum disorders (ASD), bipolar disorder (BD), and healthy individuals. This study used Similarity Network Fusion (SNF), a novel data-driven approach, to identify participant similarity networks based on relationships among demographic, brain imaging, and behavioral data. T1-weighted and diffusion-weighted magnetic resonance images were obtained for 174 adolescents and young adults (aged 16-35 years) with an SSD (n=51), an ASD without intellectual disability (n=38), euthymic BD (n=34), and healthy controls (n=51). A battery of social cognitive and neurocognitive tasks were administered. Data integration, cluster determination, and biological group formation were then obtained using SNF. We identified four new groups of individuals, each with distinct neural circuit-cognitive profiles. The most influential variables driving the formation of the new groups were robustly reliable across embedded resampling techniques. The data-driven groups showed considerably greater differentiation on key social and neurocognitive circuit nodes than groups generated by diagnostic analyses or dimensional social cognitive analyses. The data-driven groups were validated through functional outcome and brain network property measures not included in the SNF model. Cutting across diagnostic boundaries, our approach can effectively identify new groups of people based on a profile of neuroimaging and behavioral data. Our findings bring us closer to disease subtyping that can be leveraged toward the targeting of specific neural circuitry among participant subgroups to ameliorate social cognitive and neurocognitive deficits.Neuropsychopharmacology advance online publication, 6 December; doi:10.1038/npp.2017.274.
Marek Wartenberg, Joseph Schornak, Katie Gandomi, Paulo Carvalho, Chris Nycz, Niravkumar Patel, Iulian Iordachita, Clare Tempany, Nobuhiko Hata, Junichi Tokuda, and Gregory S. Fischer. 2018. “Closed-Loop Active Compensation for Needle Deflection and Target Shift During Cooperatively Controlled Robotic Needle Insertion.” Ann Biomed Eng, 46, 10, Pp. 1582-94.Abstract
Intra-operative imaging is sometimes available to assist needle biopsy, but typical open-loop insertion does not account for unmodeled needle deflection or target shift. Closed-loop image-guided compensation for deviation from an initial straight-line trajectory through rotational control of an asymmetric tip can reduce targeting error. Incorporating robotic closed-loop control often reduces physician interaction with the patient, but by pairing closed-loop trajectory compensation with hands-on cooperatively controlled insertion, a physician's control of the procedure can be maintained while incorporating benefits of robotic accuracy. A series of needle insertions were performed with a typical 18G needle using closed-loop active compensation under both fully autonomous and user-directed cooperative control. We demonstrated equivalent improvement in accuracy while maintaining physician-in-the-loop control with no statistically significant difference (p > 0.05) in the targeting accuracy between any pair of autonomous or individual cooperative sets, with average targeting accuracy of 3.56 mm. With cooperatively controlled insertions and target shift between 1 and 10 mm introduced upon needle contact, the system was able to effectively compensate up to the point where error approached a maximum curvature governed by bending mechanics. These results show closed-loop active compensation can enhance targeting accuracy, and that the improvement can be maintained under user directed cooperative insertion.
Elmira Hassanzadeh, Francesco Alessandrino, Olutayo I Olubiyi, Daniel I Glazer, Robert V. Mulkern, Andriy Fedorov, Clare M Tempany, and Fiona M Fennessy. 2018. “Comparison of Quantitative Apparent Diffusion Coefficient Parameters with Prostate Imaging Reporting and Data System V2 Assessment for Detection of Clinically Significant Peripheral Zone Prostate Cancer.” Abdom Radiol (NY), 43, 5, Pp. 1237-44.Abstract
PURPOSE: To compare diagnostic performance of PI-RADSv2 with ADC parameters to identify clinically significant prostate cancer (csPC) and to determine the impact of csPC definitions on diagnostic performance of ADC and PI-RADSv2. METHODS: We retrospectively identified treatment-naïve pathology-proven peripheral zone PC patients who underwent 3T prostate MRI, using high b-value diffusion-weighted imaging from 2011 to 2015. Using 3D slicer, areas of suspected tumor (T) and normal tissue (N) on ADC (b = 0, 1400) were outlined volumetrically. Mean ADCT, mean ADCN, ADCratio (ADCT/ADCN) were calculated. PI-RADSv2 was assigned. Three csPC definitions were used: (A) Gleason score (GS) ≥ 4 + 3; (B) GS ≥ 3 + 4; (C) MRI-based tumor volume >0.5 cc. Performances of ADC parameters and PI-RADSv2 in identifying csPC were measured using nonparametric comparison of receiver operating characteristic curves using the area under the curve (AUC). RESULTS: Eighty five cases met eligibility requirements. Diagnostic performances (AUC) in identifying csPC using three definitions were: (A) ADCT (0.83) was higher than PI-RADSv2 (0.65, p = 0.006); (B) ADCT (0.86) was higher than ADCratio (0.68, p < 0.001), and PI-RADSv2 (0.70, p = 0.04); (C) PI-RADSv2 (0.73) performed better than ADCratio (0.56, p = 0.02). ADCT performance was higher when csPC was defined by A or B versus C (p = 0.038 and p = 0.01, respectively). ADCratio performed better when csPC was defined by A versus C (p = 0.01). PI-RADSv2 performance was not affected by csPC definition. CONCLUSIONS: When csPC was defined by GS, ADC parameters provided better csPC discrimination than PI-RADSv2, with ADCT providing best result. When csPC was defined by MRI-calculated volume, PI-RADSv2 provided better discrimination than ADCratio. csPC definition did not affect PI-RADSv2 diagnostic performance.
Valerie J Sydnor, Ana María Rivas-Grajales, Amanda E Lyall, Fan Zhang, Sylvain Bouix, Sarina Karmacharya, Martha E Shenton, Carl-Fredrik Westin, Nikos Makris, Demian Wassermann, Lauren J O'Donnell, and Marek Kubicki. 2018. “A Comparison of Three Fiber Tract Delineation Methods and their Impact on White Matter Analysis.” Neuroimage, 178, Pp. 318-31.Abstract
Diffusion magnetic resonance imaging (dMRI) is an important method for studying white matter connectivity in the brain in vivo in both healthy and clinical populations. Improvements in dMRI tractography algorithms, which reconstruct macroscopic three-dimensional white matter fiber pathways, have allowed for methodological advances in the study of white matter; however, insufficient attention has been paid to comparing post-tractography methods that extract white matter fiber tracts of interest from whole-brain tractography. Here we conduct a comparison of three representative and conceptually distinct approaches to fiber tract delineation: 1) a manual multiple region of interest-based approach, 2) an atlas-based approach, and 3) a groupwise fiber clustering approach, by employing methods that exemplify these approaches to delineate the arcuate fasciculus, the middle longitudinal fasciculus, and the uncinate fasciculus in 10 healthy male subjects. We enable qualitative comparisons across methods, conduct quantitative evaluations of tract volume, tract length, mean fractional anisotropy, and true positive and true negative rates, and report measures of intra-method and inter-method agreement. We discuss methodological similarities and differences between the three approaches and the major advantages and drawbacks of each, and review research and clinical contexts for which each method may be most apposite. Emphasis is given to the means by which different white matter fiber tract delineation approaches may systematically produce variable results, despite utilizing the same input tractography and reliance on similar anatomical knowledge.
Fredrik Langkilde, Thiele Kobus, Andriy Fedorov, Ruth Dunne, Clare Tempany, Robert V. Mulkern, and Stephan E. Maier. 2018. “Evaluation of Fitting Models for Prostate Tissue Characterization using Extended-range b-factor Diffusion-weighted Imaging.” Magn Reson Med, 79, 4, Pp. 2346-58.Abstract
PURPOSE: To compare the fitting and tissue discrimination performance of biexponential, kurtosis, stretched exponential, and gamma distribution models for high b-factor diffusion-weighted images in prostate cancer. METHODS: Diffusion-weighted images with 15 b-factors ranging from b = 0 to 3500 s/mmwere obtained in 62 prostate cancer patients. Pixel-wise signal decay fits for each model were evaluated with the Akaike Information Criterion (AIC). Parameter values for each model were determined within normal prostate and the index lesion. Their potential to differentiate normal from cancerous tissue was investigated through receiver operating characteristic analysis and comparison with Gleason score. RESULTS: The biexponential slow diffusion fraction f, the apparent kurtosis diffusion coefficient ADC, and the excess kurtosis factor K differ significantly among normal peripheral zone (PZ), normal transition zone (TZ), tumor PZ, and tumor TZ. Biexponential and gamma distribution models result in the lowest AIC, indicating a superior fit. Maximum areas under the curve (AUCs) of all models ranged from 0.93 to 0.96 for the PZ and from 0.95 to 0.97 for the TZ. Similar AUCs also result from the apparent diffusion coefficient (ADC) of a monoexponential fit to a b-factor sub-range up to 1250 s/mm. For kurtosis and stretched exponential models, single parameters yield the highest AUCs, whereas for the biexponential and gamma distribution models, linear combinations of parameters produce the highest AUCs. Parameters with high AUC show a trend in differentiating low from high Gleason score, whereas parameters with low AUC show no such ability. CONCLUSION: All models, including a monoexponential fit to a lower-b sub-range, achieve similar AUCs for discrimination of normal and cancer tissue. The biexponential model, which is favored statistically, also appears to provide insight into disease-related microstructural changes. Magn Reson Med 79:2346-2358, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Pedro Moreira, Niravkumar Patel, Marek Wartenberg, Gang Li, Kemal Tuncali, Tamas Heffter, Everette C Burdette, Iulian Iordachita, Gregory S. Fischer, Nobuhiko Hata, Clare MC Tempany, and Junichi Tokuda. 2018. “Evaluation of Robot-assisted MRI-guided Prostate Biopsy: Needle Path Analysis during Clinical Trials.” Phys Med Biol, 63, 20, Pp. 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.
Jie Luo, Matthew Toews, Inês Machado, Sarah Frisken, Miaomiao Zhang, Frank Preiswerk, Alireza Sedghi, Hongyi Ding, Steve Pieper, Polina Golland, Alexandra Golby, Masashi Sugiyama, and William III M Wells. 2018. “A Feature-Driven Active Framework for Ultrasound-Based Brain Shift Compensation.” In MICCAI 2018, LNCS 11073: Pp. 30-38. Springer.Abstract
A reliable Ultrasound (US)-to-US registration method to compensate for brain shift would substantially improve Image-Guided Neurological Surgery. Developing such a registration method is very challenging, due to factors such as the tumor resection, the complexity of brain pathology and the demand for fast computation. We propose a novel feature-driven active registration framework. Here, landmarks and their displacement are first estimated from a pair of US images using corresponding local image features. Subsequently, a Gaussian Process (GP) model is used to interpolate a dense deformation field from the sparse landmarks. Kernels of the GP are estimated by using variograms and a discrete grid search method. If necessary, the user can actively add new landmarks based on the image context and visualization of the uncertainty measure provided by the GP to further improve the result. We retrospectively demonstrate our registration framework as a robust and accurate brain shift compensation solution on clinical data.
Luo MICCAI 2018
Shun Gong, Fan Zhang, Isaiah Norton, Walid I Essayed, Prashin Unadkat, Laura Rigolo, Ofer Pasternak, Yogesh Rathi, Lijun Hou, Alexandra J Golby, and Lauren J O'Donnell. 2018. “Free Water Modeling of Peritumoral Edema using Multi-fiber Tractography: Application to Tracking the Arcuate Fasciculus for Neurosurgical Planning.” PLoS One, 13, 5, Pp. e0197056.Abstract
PURPOSE: Peritumoral edema impedes the full delineation of fiber tracts due to partial volume effects in image voxels that contain a mixture of cerebral parenchyma and extracellular water. The purpose of this study is to investigate the effect of incorporating a free water (FW) model of edema for white matter tractography in the presence of edema. MATERIALS AND METHODS: We retrospectively evaluated 26 consecutive brain tumor patients with diffusion MRI and T2-weighted images acquired presurgically. Tractography of the arcuate fasciculus (AF) was performed using the two-tensor unscented Kalman filter tractography (UKFt) method, the UKFt method with a reduced fiber tracking stopping fractional anisotropy (FA) threshold (UKFt+rFA), and the UKFt method with the addition of a FW compartment (UKFt+FW). An automated white matter fiber tract identification approach was applied to delineate the AF. Quantitative measurements included tract volume, edema volume, and mean FW fraction. Visual comparisons were performed by three experts to evaluate the quality of the detected AF tracts. RESULTS: The AF volume in edematous brain hemispheres was significantly larger using the UKFt+FW method (p<0.0001) compared to UKFt, but not significantly larger (p = 0.0996) in hemispheres without edema. The AF size increase depended on the volume of edema: a significant correlation was found between AF volume affected by (intersecting) edema and AF volume change with the FW model (Pearson r = 0.806, p<0.0001). The mean FW fraction was significantly larger in tracts intersecting edema (p = 0.0271). Compared to the UKFt+rFA method, there was a significant increase of the volume of the AF tract that intersected the edema using the UKFt+FW method, while the whole AF volumes were similar. Expert judgment results, based on the five patients with the smallest AF volumes, indicated that the expert readers generally preferred the AF tract obtained by using the FW model, according to their anatomical knowledge and considering the potential influence of the final results on the surgical route. CONCLUSION: Our results indicate that incorporating biophysical models of edema can increase the sensitivity of tractography in regions of peritumoral edema, allowing better tract visualization in patients with high grade gliomas and metastases.
Yi Hong, Lauren J O'Donnell, Peter Savadjiev, Fan Zhang, Demian Wassermann, Ofer Pasternak, Hans Johnson, Jane Paulsen, Jean-Paul Vonsattel, Nikos Makris, Carl F Westin, and Yogesh Rathi. 2018. “Genetic Load Determines Atrophy in Hand Cortico-striatal Pathways in Presymptomatic Huntington's Disease.” Hum Brain Mapp, 39, 10, Pp. 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.
Angela Albi, Antonio Meola, Fan Zhang, Pegah Kahali, Laura Rigolo, Chantal MW Tax, Pelin Aksit Ciris, Walid I Essayed, Prashin Unadkat, Isaiah Norton, Yogesh Rathi, Olutayo Olubiyi, Alexandra J Golby, and Lauren J O'Donnell. 2018. “Image Registration to Compensate for EPI Distortion in Patients with Brain Tumors: An Evaluation of Tract-Specific Effects.” J Neuroimaging, 28, 2, Pp. 173-82.Abstract
BACKGROUND AND PURPOSE: Diffusion magnetic resonance imaging (dMRI) provides preoperative maps of neurosurgical patients' white matter tracts, but these maps suffer from echo-planar imaging (EPI) distortions caused by magnetic field inhomogeneities. In clinical neurosurgical planning, these distortions are generally not corrected and thus contribute to the uncertainty of fiber tracking. Multiple image processing pipelines have been proposed for image-registration-based EPI distortion correction in healthy subjects. In this article, we perform the first comparison of such pipelines in neurosurgical patient data. METHODS: Five pipelines were tested in a retrospective clinical dMRI dataset of 9 patients with brain tumors. Pipelines differed in the choice of fixed and moving images and the similarity metric for image registration. Distortions were measured in two important tracts for neurosurgery, the arcuate fasciculus and corticospinal tracts. RESULTS: Significant differences in distortion estimates were found across processing pipelines. The most successful pipeline used dMRI baseline and T2-weighted images as inputs for distortion correction. This pipeline gave the most consistent distortion estimates across image resolutions and brain hemispheres. CONCLUSIONS: Quantitative results of mean tract distortions on the order of 1-2 mm are in line with other recent studies, supporting the potential need for distortion correction in neurosurgical planning. Novel results include significantly higher distortion estimates in the tumor hemisphere and greater effect of image resolution choice on results in the tumor hemisphere. Overall, this study demonstrates possible pitfalls and indicates that care should be taken when implementing EPI distortion correction in clinical settings.
Markus D Herrmann, David A Clunie, Andriy Fedorov, Sean W Doyle, Steven Pieper, Veronica Klepeis, Long P Le, George L Mutter, David S Milstone, Thomas J Schultz, Ron Kikinis, Gopal K Kotecha, David H Hwang, Katherine P Andriole, John A Iafrate, James A Brink, Giles W Boland, Keith J Dreyer, Mark Michalski, Jeffrey A Golden, David N Louis, and Jochen K Lennerz. 2018. “Implementing the DICOM Standard for Digital Pathology.” J Pathol Inform, 9, Pp. 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.
Shelley Hualei Zhang, Stephan E. Maier, and Lawrence P. Panych. 2018. “Improved Spatial Localization in Magnetic Resonance Spectroscopic Imaging with Two-dimensional PSF-Choice Encoding.” J Magn Reson, 290, Pp. 18-28.Abstract
PURPOSE: Magnetic resonance spectroscopic imaging (MRSI), under low-spatial resolution settings, often suffers signal contamination from neighboring voxels due to ringing artifacts. Spatial localization can be improved by constraining the point-spread-function (PSF). Here the effectiveness of the two-dimensional PSF-Choice technique in providing improved spatial localization for MRSI is demonstrated. THEORY AND METHODS: The PSF-Choice technique constrains the PSF to a desired shape by manipulating the weighting of RF excitation pulse throughout phase-encode steps. Based on a Point REsolved SpectroScopy (PRESS)-type sequence, PSF-Choice encoding was implemented along two dimensions to excite a two-dimensional Gaussian profile, by replacing the usual RF excitation pulse with a train of pulses that is modified at each phase-encoding step. The method was proven mathematically, and demonstrated experimentally in phantoms containing prostate relevant metabolic compounds of choline, creatine and citrate. RESULTS: Using a dedicated prostate-mimicking spectroscopy phantom surrounded by oil, it was found that there is significantly less signal contamination from oil for PSF-Choice encoding compared with standard phase encoding. In particular, with standard phase encoding, there was a significant difference (p = 0.014) between ratios of Choline + Creatine to Citrate for voxels well within the phantom compared to voxels within the phantom but near the boundary with oil. The ratios in boundary voxels were also significantly different (p = 0.035) from reference values obtained using the prostate phantom with no oil present. In contrast, no significant differences were found in comparisons of these ratios when encoding with PSF-Choice. CONCLUSION: The PSF-Choice scheme applied along two dimensions produces MR spectroscopic images with substantially reduced truncation artifacts and spectral contamination.
Sankha S Basu, Elizabeth C Randall, Michael S Regan, Begoña GC Lopez, Amanda R Clark, Nicholas D Schmitt, Jeffrey N Agar, Deborah A Dillon, and Nathalie YR Agar. 2018. “In Vitro Liquid Extraction Surface Analysis Mass Spectrometry (ivLESA-MS) for Direct Metabolic Analysis of Adherent Cells in Culture.” Anal Chem, 90, 8, Pp. 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.
Evren Özarslan, Cem Yolcu, Magnus Herberthson, Hans Knutsson, and Carl-Fredrik Westin. 2018. “Influence of the Size and Curvedness of Neural Projections on the Orientationally Averaged Diffusion MR Signal.” Front Phys, 6.Abstract
Neuronal and glial projections can be envisioned to be tubes of infinitesimal diameter as far as diffusion magnetic resonance (MR) measurements via clinical scanners are concerned. Recent experimental studies indicate that the decay of the orientationally-averaged signal in white-matter may be characterized by the power-law, () ∝ , where is the wavenumber determined by the parameters of the pulsed field gradient measurements. One particular study by McKinnon . [1] reports a distinctively faster decay in gray-matter. Here, we assess the role of the size and curvature of the neurites and glial arborizations in these experimental findings. To this end, we studied the signal decay for diffusion along general curves at all three temporal regimes of the traditional pulsed field gradient measurements. We show that for curvy projections, employment of longer pulse durations leads to a disappearance of the decay, while such decay is robust when narrow gradient pulses are used. Thus, in clinical acquisitions, the lack of such a decay for a fibrous specimen can be seen as indicative of fibers that are curved. We note that the above discussion is valid for an intermediate range of -values as the true asymptotic behavior of the signal decay is () ∝ for narrow pulses (through Debye-Porod law) or steeper for longer pulses. This study is expected to provide insights for interpreting the diffusion-weighted images of the central nervous system and aid in the design of acquisition strategies.
Elizabeth C Randall, Kristina B Emdal, Janice K Laramy, Minjee Kim, Alison Roos, David Calligaris, Michael S Regan, Shiv K Gupta, Ann C Mladek, Brett L Carlson, Aaron J Johnson, Fa-Ke Lu, Sunney X Xie, Brian A Joughin, Raven J Reddy, Sen Peng, Walid M Abdelmoula, Pamela R Jackson, Aarti Kolluri, Katherine A. Kellersberger, Jeffrey N Agar, Douglas A Lauffenburger, Kristin R Swanson, Nhan L Tran, William F Elmquist, Forest M White, Jann N Sarkaria, and Nathalie YR Agar. 2018. “Integrated Mapping of Pharmacokinetics and Pharmacodynamics in a Patient-derived Xenograft Model of Glioblastoma.” Nat Commun, 9, 1, Pp. 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.

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