Publications

2018
Malyarenko D, Fedorov A, Bell L, Prah M, Hectors S, Arlinghaus L, Muzi M, Solaiyappan M, Jacobs M, Fung M, et al. Toward Uniform Implementation of Parametric Map Digital Imaging and Communication in Medicine Standard in Multisite Quantitative Diffusion Imaging Studies. J Med Imaging (Bellingham). 2018;5 (1) :011006.Abstract
This paper reports on results of a multisite collaborative project launched by the MRI subgroup of Quantitative Imaging Network to assess current capability and provide future guidelines for generating a standard parametric diffusion map Digital Imaging and Communication in Medicine (DICOM) in clinical trials that utilize quantitative diffusion-weighted imaging (DWI). Participating sites used a multivendor DWI DICOM dataset of a single phantom to generate parametric maps (PMs) of the apparent diffusion coefficient (ADC) based on two models. The results were evaluated for numerical consistency among models and true phantom ADC values, as well as for consistency of metadata with attributes required by the DICOM standards. This analysis identified missing metadata descriptive of the sources for detected numerical discrepancies among ADC models. Instead of the DICOM PM object, all sites stored ADC maps as DICOM MR objects, generally lacking designated attributes and coded terms for quantitative DWI modeling. Source-image reference, model parameters, ADC units and scale, deemed important for numerical consistency, were either missing or stored using nonstandard conventions. Guided by the identified limitations, the DICOM PM standard has been amended to include coded terms for the relevant diffusion models. Open-source software has been developed to support conversion of site-specific formats into the standard representation.
Kim AJ, Basu S, Glass C, Ross EL, Agar N, He Q, Calligaris D. Unique Intradural Inflammatory Mass Containing Precipitated Morphine: Confirmatory Analysis by LESA-MS and MALDI-MS. Pain Pract. 2018;18 (7) :889-94.Abstract
Opioids are often used for analgesia via continuous intrathecal delivery by implantable devices. A higher concentration and daily dose of opioid have been postulated as risk factors for intrathecal granuloma formation. We present a 42-year-old female patient with chronic abdominal pain from refractory pancreatitis, with an intrathecal drug delivery device implanted 21 years prior, delivering continuous intrathecal morphine. After many years without concerning physical signs or complaints, with gradual increases in daily morphine dose, she presented with rapidly progressive neurologic deficits, including lower extremity, bladder, and bowel symptoms. These symptoms were determined to be secondary to mass effect and local inflammation related to an intrathecal catheter tip granuloma, detected on magnetic resonance imaging of the spine. The mass was urgently resected. On histopathologic examination, this granuloma was found to be unique, in that in addition to the expected inflammatory components, it appeared to contain precipitated nonpolarizable crystals. These were identified as precipitated morphine using liquid extraction surface analysis-tandem mass spectrometry (LESA-MS/MS) and matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance-mass spectrometry imaging (MALDI-FTICR-MSI). In addition to the unique finding of precipitated morphine crystals, the long-term follow-up of both morphine concentration and daily dose increases provides insight into the formation of intrathecal granulomas.
Özarslan E, Yolcu C, Herberthson M, Knutsson H, Westin C-F. Influence of the Size and Curvedness of Neural Projections on the Orientationally Averaged Diffusion MR Signal. Front Phys. 2018;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.
Tokuda J, Chauvin L, Ninni B, Kato T, King F, Tuncali K, Hata N. Motion Compensation for MRI-compatible Patient-mounted Needle Guide Device: Estimation of Targeting Accuracy in MRI-guided Kidney Cryoablations. Phys Med Biol. 2018;63 (8) :085010.Abstract
Patient-mounted needle guide devices for percutaneous ablation are vulnerable to patient motion. The objective of this study is to develop and evaluate a software system for an MRI-compatible patient-mounted needle guide device that can adaptively compensate for displacement of the device due to patient motion using a novel image-based automatic device-to-image registration technique. We have developed a software system for an MRI-compatible patient-mounted needle guide device for percutaneous ablation. It features fully-automated image-based device-to-image registration to track the device position, and a device controller to adjust the needle trajectory to compensate for the displacement of the device. We performed: (a) a phantom study using a clinical MR scanner to evaluate registration performance; (b) simulations using intraoperative time-series MR data acquired in 20 clinical cases of MRI-guided renal cryoablations to assess its impact on motion compensation; and (c) a pilot clinical study in three patients to test its feasibility during the clinical procedure. FRE, TRE, and success rate of device-to-image registration were [Formula: see text] mm, [Formula: see text] mm, and 98.3% for the phantom images. The simulation study showed that the motion compensation reduced the targeting error for needle placement from 8.2 mm to 5.4 mm (p  <  0.0005) in patients under general anesthesia (GA), and from 14.4 mm to 10.0 mm ([Formula: see text]) in patients under monitored anesthesia care (MAC). The pilot study showed that the software registered the device successfully in a clinical setting. Our simulation study demonstrated that the software system could significantly improve targeting accuracy in patients treated under both MAC and GA. Intraprocedural image-based device-to-image registration was feasible.
Zhang SH, Maier SE, Panych LP. Improved Spatial Localization in Magnetic Resonance Spectroscopic Imaging with Two-dimensional PSF-Choice Encoding. J Magn Reson. 2018;290 :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.
Langkilde F, Kobus T, Fedorov A, Dunne R, Tempany C, Mulkern RV, Maier SE. Evaluation of Fitting Models for Prostate Tissue Characterization using Extended-range b-factor Diffusion-weighted Imaging. Magn Reson Med. 2018;79 (4) :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.
Albi A, Meola A, Zhang F, Kahali P, Rigolo L, Tax CMW, Ciris PA, Essayed WI, Unadkat P, Norton I, et al. Image Registration to Compensate for EPI Distortion in Patients with Brain Tumors: An Evaluation of Tract-Specific Effects. J Neuroimaging. 2018;28 (2) :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.
Nilsson M, Larsson J, Lundberg D, Szczepankiewicz F, Witzel T, Westin C-F, Bryskhe K, Topgaard D. Liquid Crystal Phantom for Validation of Microscopic Diffusion Anisotropy Measurements on Clinical MRI Systems. Magn Reson Med. 2018;79 (3) :1817-28.Abstract
PURPOSE: To develop a phantom for validating MRI pulse sequences and data processing methods to quantify microscopic diffusion anisotropy in the human brain. METHODS: Using a liquid crystal consisting of water, detergent, and hydrocarbon, we designed a 0.5-L spherical phantom showing the theoretically highest possible degree of microscopic anisotropy. Data were acquired on the Connectome scanner using echo-planar imaging signal readout and diffusion encoding with axisymmetric b-tensors of varying magnitude, anisotropy, and orientation. The mean diffusivity, fractional anisotropy (FA), and microscopic FA (µFA) parameters were estimated. RESULTS: The phantom was observed to have values of mean diffusivity similar to brain tissue, and relaxation times compatible with echo-planar imaging echo times on the order of 100 ms. The estimated values of µFA were at the theoretical maximum of 1.0, whereas the values of FA spanned the interval from 0.0 to 0.8 as a result of varying orientational order of the anisotropic domains within each voxel. CONCLUSIONS: The proposed phantom can be manufactured by mixing three widely available chemicals in volumes comparable to a human head. The acquired data are in excellent agreement with theoretical predictions, showing that the phantom is ideal for validating methods for measuring microscopic diffusion anisotropy on clinical MRI systems. Magn Reson Med 79:1817-1828, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Schmidt EJ, Halperin HR. MRI use for Atrial Tissue Characterization in Arrhythmias and for EP Procedure Guidance. Int J Cardiovasc Imaging. 2018;34 (1) :81-95.Abstract
We review the utilization of magnetic resonance imaging methods for classifying atrial tissue properties that act as a substrate for common cardiac arrhythmias, such as atrial fibrillation. We then review state-of-the-art methods for mapping this substrate as a predicate for treatment, as well as methods used to ablate the electrical pathways that cause arrhythmia and restore patients to sinus rhythm.
Jiang B, Gao W, Kacher D, Nevo E, Fetics B, Lee TC, Jayender J. Kalman Filter-based EM-optical Sensor Fusion for Needle Deflection Estimation. Int J Comput Assist Radiol Surg. 2018;13 (4) :573-83.Abstract
PURPOSE: In many clinical procedures such as cryoablation that involves needle insertion, accurate placement of the needle's tip at the desired target is the major issue for optimizing the treatment and minimizing damage to the neighboring anatomy. However, due to the interaction force between the needle and tissue, considerable error in intraoperative tracking of the needle tip can be observed as needle deflects. METHODS: In this paper, measurements data from an optical sensor at the needle base and a magnetic resonance (MR) gradient field-driven electromagnetic (EM) sensor placed 10 cm from the needle tip are used within a model-integrated Kalman filter-based sensor fusion scheme. Bending model-based estimations and EM-based direct estimation are used as the measurement vectors in the Kalman filter, thus establishing an online estimation approach. RESULTS: Static tip bending experiments show that the fusion method can reduce the mean error of the tip position estimation from 29.23 mm of the optical sensor-based approach to 3.15 mm of the fusion-based approach and from 39.96 to 6.90 mm, at the MRI isocenter and the MRI entrance, respectively. CONCLUSION: This work established a novel sensor fusion scheme that incorporates model information, which enables real-time tracking of needle deflection with MRI compatibility, in a free-hand operating setup.
Zhang F, Wu W, Ning L, McAnulty G, Waber D, Gagoski B, Sarill K, Hamoda HM, Song Y, Cai W, et al. Suprathreshold Fiber Cluster Statistics: Leveraging White Matter Geometry to Enhance Tractography Statistical Analysis. Neuroimage. 2018;171 :341-54.Abstract
This work presents a suprathreshold fiber cluster (STFC) method that leverages the whole brain fiber geometry to enhance statistical group difference analyses. The proposed method consists of 1) a well-established study-specific data-driven tractography parcellation to obtain white matter tract parcels and 2) a newly proposed nonparametric, permutation-test-based STFC method to identify significant differences between study populations. The basic idea of our method is that a white matter parcel's neighborhood (nearby parcels with similar white matter anatomy) can support the parcel's statistical significance when correcting for multiple comparisons. We propose an adaptive parcel neighborhood strategy to allow suprathreshold fiber cluster formation that is robust to anatomically varying inter-parcel distances. The method is demonstrated by application to a multi-shell diffusion MRI dataset from 59 individuals, including 30 attention deficit hyperactivity disorder patients and 29 healthy controls. Evaluations are conducted using both synthetic and in-vivo data. The results indicate that the STFC method gives greater sensitivity in finding group differences in white matter tract parcels compared to several traditional multiple comparison correction methods.
Toews M, Wells WM. Phantomless Auto-Calibration and Online Calibration Assessment for a Tracked Freehand 2-D Ultrasound Probe. IEEE Trans Med Imaging. 2018;37 (1) :262-72.Abstract
This paper presents a method for automatically calibrating and assessing the calibration quality of an externally tracked 2-D ultrasound (US) probe by scanning arbitrary, natural tissues, as opposed a specialized calibration phantom as is the typical practice. A generative topic model quantifies the posterior probability of calibration parameters conditioned on local 2-D image features arising from a generic underlying substrate. Auto-calibration is achieved by identifying the maximum a-posteriori image-to-probe transform, and calibration quality is assessed online in terms of the posterior probability of the current image-to-probe transform. Both are closely linked to the 3-D point reconstruction error (PRE) in aligning feature observations arising from the same underlying physical structure in different US images. The method is of practical importance in that it operates simply by scanning arbitrary textured echogenic structures, e.g., in-vivo tissues in the context of the US-guided procedures, without requiring specialized calibration procedures or equipment. Observed data take the form of local scale-invariant features that can be extracted and fit to the model in near real-time. Experiments demonstrate the method on a public data set of in vivo human brain scans of 14 unique subjects acquired in the context of neurosurgery. Online calibration assessment can be performed at approximately 3 Hz for the US images of pixels. Auto-calibration achieves an internal mean PRE of 1.2 mm and a discrepancy of [2 mm, 6 mm] in comparison to the calibration via a standard phantom-based method.
Black D, Unger M, Fischer N, Kikinis R, Hahn H, Neumuth T, Glaser B. Auditory Display as Feedback for a Novel Eye-tracking System for Sterile Operating Room Interaction. Int J Comput Assist Radiol Surg. 2018;13 (1) :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.
Black D, Hahn HK, Kikinis R, Wårdell K, Haj-Hosseini N. Auditory Display for Fluorescence-guided Open Brain Tumor Surgery. Int J Comput Assist Radiol Surg. 2018;13 (1) :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.
Abayazid M, Kato T, Silverman SG, Hata N. Using Needle Orientation Sensing as Surrogate Signal for Respiratory Motion Estimation in Rercutaneous Interventions. Int J Comput Assist Radiol Surg. 2018;13 (1) :125-33.Abstract
PURPOSE: To develop and evaluate an approach to estimate the respiratory-induced motion of lesions in the chest and abdomen. MATERIALS AND METHODS: The proposed approach uses the motion of an initial reference needle inserted into a moving organ to estimate the lesion (target) displacement that is caused by respiration. The needles position is measured using an inertial measurement unit (IMU) sensor externally attached to the hub of an initially placed reference needle. Data obtained from the IMU sensor and the target motion are used to train a learning-based approach to estimate the position of the moving target. An experimental platform was designed to mimic respiratory motion of the liver. Liver motion profiles of human subjects provided inputs to the experimental platform. Variables including the insertion angle, target depth, target motion velocity and target proximity to the reference needle were evaluated by measuring the error of the estimated target position and processing time. RESULTS: The mean error of estimation of the target position ranged between 0.86 and 1.29 mm. The processing maximum training and testing time was 5 ms which is suitable for real-time target motion estimation using the needle position sensor. CONCLUSION: The external motion of an initially placed reference needle inserted into a moving organ can be used as a surrogate, measurable and accessible signal to estimate in real-time the position of a moving target caused by respiration; this technique could then be used to guide the placement of subsequently inserted needles directly into the target.
Stefanik L, Erdman L, Ameis SH, Foussias G, Mulsant BH, Behdinan T, Goldenberg A, O'Donnell LJ, Voineskos AN. Brain-Behavior Participant Similarity Networks Among Youth and Emerging Adults with Schizophrenia Spectrum, Autism Spectrum, or Bipolar Disorder and Matched Controls. Neuropsychopharmacology. 2018;43 (5) :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.
Zhang F, Savadjiev P, Cai W, Song Y, Rathi Y, Tunç B, Parker D, Kapur T, Schultz RT, Makris N, et al. Whole Brain White Matter Connectivity Analysis using Machine Learning: An Application to Autism. Neuroimage. 2018;172 :826-37.Abstract
In this paper, we propose an automated white matter connectivity analysis method for machine learning classification and characterization of white matter abnormality via identification of discriminative fiber tracts. The proposed method uses diffusion MRI tractography and a data-driven approach to find fiber clusters corresponding to subdivisions of the white matter anatomy. Features extracted from each fiber cluster describe its diffusion properties and are used for machine learning. The method is demonstrated by application to a pediatric neuroimaging dataset from 149 individuals, including 70 children with autism spectrum disorder (ASD) and 79 typically developing controls (TDC). A classification accuracy of 78.33% is achieved in this cross-validation study. We investigate the discriminative diffusion features based on a two-tensor fiber tracking model. We observe that the mean fractional anisotropy from the second tensor (associated with crossing fibers) is most affected in ASD. We also find that local along-tract (central cores and endpoint regions) differences between ASD and TDC are helpful in differentiating the two groups. These altered diffusion properties in ASD are associated with multiple robustly discriminative fiber clusters, which belong to several major white matter tracts including the corpus callosum, arcuate fasciculus, uncinate fasciculus and aslant tract; and the white matter structures related to the cerebellum, brain stem, and ventral diencephalon. These discriminative fiber clusters, a small part of the whole brain tractography, represent the white matter connections that could be most affected in ASD. Our results indicate the potential of a machine learning pipeline based on white matter fiber clustering.
Trinh TW, Glazer DI, Sadow CA, Sahni AV, Geller NL, Silverman SG. Bladder Cancer Diagnosis with CT Urography: Test Characteristics and Reasons for False-positive and False-negative Results. Abdom Radiol (NY). 2018;43 (3) :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.
Hassanzadeh E, Alessandrino F, Olubiyi OI, Glazer DI, Mulkern RV, Fedorov A, Tempany CM, Fennessy FM. 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). 2018;43 (5) :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.
2017
Chennubhotla C, Clarke LP, Fedorov A, Foran D, Harris G, Helton E, Nordstrom R, Prior F, Rubin D, Saltz JH, et al. An Assessment of Imaging Informatics for Precision Medicine in Cancer. Yearb Med Inform. 2017;26 (1) :110-9.Abstract
Precision medicine requires the measurement, quantification, and cataloging of medical characteristics to identify the most effective medical intervention. However, the amount of available data exceeds our current capacity to extract meaningful information. We examine the informatics needs to achieve precision medicine from the perspective of quantitative imaging and oncology. The National Cancer Institute (NCI) organized several workshops on the topic of medical imaging and precision medicine. The observations and recommendations are summarized herein. Recommendations include: use of standards in data collection and clinical correlates to promote interoperability; data sharing and validation of imaging tools; clinician's feedback in all phases of research and development; use of open-source architecture to encourage reproducibility and reusability; use of challenges which simulate real-world situations to incentivize innovation; partnership with industry to facilitate commercialization; and education in academic communities regarding the challenges involved with translation of technology from the research domain to clinical utility and the benefits of doing so. This article provides a survey of the role and priorities for imaging informatics to help advance quantitative imaging in the era of precision medicine. While these recommendations were drawn from oncology, they are relevant and applicable to other clinical domains where imaging aids precision medicine.

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