Medicine and Health Sciences Commons^™

Development Of A Measure Of Model Fidelity For Mental Health Crisis Resolution Teams, Brynmor Lloyd-Evans, Gary R. Bond, Torleif Ruud, Ada Ivanecka

Dartmouth Scholarship

Crisis Resolution Teams (CRTs) provide short-term intensive home treatment to people experiencing mental health crisis. Trial evidence suggests CRTs can be effective at reducing hospital admissions and increasing satisfaction with acute care. When scaled up to national level however, CRT implementation and outcomes have been variable. We aimed to develop and test a fidelity scale to assess adherence to a model of best practice for CRTs, based on best available evidence.

Logarithmic Intensity Compression In Fluorescence Guided Surgery Applications, Alisha V. Dsouza, Huiyun Lin, Jason Gunn, Brian W. Pogue

Dartmouth Scholarship

The use of fluorescence video imaging to guide surgery is rapidly expanding, and improvements in camera readout dynamic range have not matched display capabilities. Logarithmic intensity compression is a fast, single-step mapping technique that can map the useable dynamic range of high-bit fluorescence images onto the typical 8-bit display and potentially be a variable dynamic contrast enhancement tool. We demonstrate a ∼4.6  times improvement in image quality quantified by image entropy and a dynamic range reduction by a factor of ∼380 by the use of log-compression tools in processing in vivo fluorescence images.

Molecular Dyes Used For Surgical Specimen Margin Orientation Allow For Intraoperative Optical Assessment During Breast Conserving Surgery, David M. Mcclatchy, Venkataramanan Krishnaswamy, Stephen C. Kanick, Jonathan T. Elliott, Wendy A. Wells, Richard J. Barth Jr., Keith D. Paulsen, Brian W. Pogue

Dartmouth Scholarship

A variety of optical techniques utilizing near-infrared (NIR) light are being proposed for intraoperative breast tumor margin assessment. However, immediately following a lumpectomy excision, the margins are inked, which preserves the orientation of the specimen but prevents optical interrogation of the tissue margins. Here, a workflow is proposed that allows for both NIR optical assessment following full specimen marking using molecular dyes which have negligible absorption and scattering in the NIR. The effect of standard surgical inks in contrast to molecular dyes for an NIR signal is shown. Further, the proposed workflow is demonstrated with full specimen intraoperative imaging on …

Acute Kidney Injury Risk Prediction In Patients Undergoing Coronary Angiography In A National Veterans Health Administration Cohort With External Validation, Jeremiah R. Brown, Todd A. Mackenzie, Thomas M. Maddox, James Fly, Thomas T. Tsai, Mary E. Plomondon, Christopher D. Nielson, Edward D. Siew, Frederic S. Resnic, Clifton R. Baker, John S. Rumsfeld, Michael E. Matheny

Dartmouth Scholarship

Background:

Acute kidney injury (AKI) occurs frequently after cardiac catheterization and percutaneous coronary intervention. Although a clinical risk model exists for percutaneous coronary intervention, no models exist for both procedures, nor do existing models account for risk factors prior to the index admission. We aimed to develop such a model for use in prospective automated surveillance programs in the Veterans Health Administration.

Methods and Results:

We collected data on all patients undergoing cardiac catheterization or percutaneous coronary intervention in the Veterans Health Administration from January 01, 2009 to September 30, 2013, excluding patients with chronic dialysis, end‐stage renal disease, renal …

Dual-Channel Red/Blue Fluorescence Dosimetry With Broadband Reflectance Spectroscopic Correction Measures Protoporphyrin Ix Production During Photodynamic Therapy Of Actinic Keratosis, Stephen Chad Kanick, Scott C. Davis, Yan Zhao, Tayyaba Hasan, Edward V. Maytin, Brian W. Pogue, M Shane Chapman

Dartmouth Scholarship

Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for …

Impact Of Treatment Response Metrics On Photodynamic Therapy Planning And Outcomes In A Three-Dimensional Model Of Ovarian Cancer, Sriram Anbil, Imran Rizvi, Jonathan P. Celli, Nermina Alagic, Brian W. Pogue, Tayyaba Hasan

Dartmouth Scholarship

Common methods to characterize treatment efficacy based on morphological imaging may misrepresent outcomes and exclude effective therapies. Using a three-dimensional model of ovarian cancer, two functional treatment response metrics are used to evaluate photodynamic therapy (PDT) efficacy: total volume, calculated from viable and nonviable cells, and live volume, calculated from viable cells. The utility of these volume-based metrics is corroborated using independent reporters of photodynamic activity: viability, a common fluorescence-based ratiometric analysis, and photosensitizer photobleaching, which is characterized by a loss of fluorescence due in part to the production of reactive species during PDT. Live volume correlated with both photobleaching …

Pilot Study Assessment Of Dynamic Vascular Changes In Breast Cancer With Near-Infrared Tomography From Prospectively Targeted Manipulations Of Inspired End-Tidal Partial Pressure Of Oxygen And Carbon Dioxide, Shudong Jiang, Brian W. Pogue, Kelly E. Michaelsen, Michael Jermyn, Michael A. Mastanduno, Tracy E. Frazee, Peter A. Kaufman, Keith D. Paulsen

Dartmouth Scholarship

The dynamic vascular changes in the breast resulting from manipulation of both inspired end-tidal partial pressure of oxygen and carbon dioxide were imaged using a 30 s per frame frequency-domain near-infrared spectral (NIRS) tomography system. By analyzing the images from five subjects with asymptomatic mammography under different inspired gas stimulation sequences, the mixture that maximized tissue vascular and oxygenation changes was established. These results indicate maximum changes in deoxy-hemoglobin, oxygen saturation, and total hemoglobin of 21, 9, and 3%, respectively. Using this inspired gas manipulation sequence, an individual case study of a subject with locally advanced breast cancer undergoing neoadjuvant …

Development Of A Diagnostic Test Set To Assess Agreement In Breast Pathology: Practical Application Of The Guidelines For Reporting Reliability And Agreement Studies (Grras), Natalia V. Oster, Patricia A. Carney, Kimberly H. Allison, Donald L. Weaver, Lisa Reisch, Gary Longton, Tracy Onega

Dartmouth Scholarship

Diagnostic test sets are a valuable research tool that contributes importantly to the validity and reliability of studies that assess agreement in breast pathology. In order to fully understand the strengths and weaknesses of any agreement and reliability study, however, the methods should be fully reported. In this paper we provide a step-by-step description of the methods used to create four complex test sets for a study of diagnostic agreement among pathologists interpreting breast biopsy specimens. We use the newly developed Guidelines for Reporting Reliability and Agreement Studies (GRRAS) as a basis to report these methods.

Scanning In Situ Spectroscopy Pplatform For Imaging Surgical Breast Tissue Specimens, Venkataramanan Krishnaswamy, Ashley M. Laughney, Wendy A. Wells, Keith D. Paulsen, Brian W. Pogue

Dartmouth Scholarship

A non-contact localized spectroscopic imaging platform has been developed and optimized to scan 1 x 1 cm² square regions of surgically resected breast tissue specimens with ~150-micron resolution. A color corrected, image-space telecentric scanning design maintained a consistent sampling geometry and uniform spot size across the entire imaging field. Theoretical modeling in ZEMAX allowed estimation of the spot size, which is equal at both the center and extreme positions of the field with ~5% variation across the designed waveband, indicating excellent color correction. The spot sizes at the center and an extreme field position were also measured experimentally using the …

Dual-Tracer Background Subtraction Approach For Fluorescent Molecular Tomography, Kenneth M. Tichauer, Robert W. Holt, Fadi El-Ghussein, Scott C. Davis, Kimberly S. Samkoe, Jason R. Gunn, Frederic Leblond, Brian W. Pogue

Dartmouth Scholarship

Diffuse fluorescence tomography requires high contrast-to-background ratios to accurately reconstruct inclusions of interest. This is a problem when imaging the uptake of fluorescently labeled molecularly targeted tracers in tissue, which can result in high levels of heterogeneously distributed background uptake. We present a dual-tracer background subtraction approach, wherein signal from the uptake of an untargeted tracer is subtracted from targeted tracer signal prior to image reconstruction, resulting in maps of targeted tracer binding. The approach is demonstrated in simulations, a phantom study, and in a mouse glioma imaging study, demonstrating substantial improvement over conventional and homogenous background subtraction image reconstruction …

Joint Effect Of Genetic And Lifestyle Risk Factors On Type 2 Diabetes Risk Among Chinese Men And Women, Raquel Villegas, Ryan Delahanty, Yu-Tang Gao, Jirong Long, Scott M. Williams, Yong-Bing Xiang, Hui Cai, Hong-Lan Li, Frank Hu, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu

Dartmouth Scholarship

More than 40 genetic susceptibility loci have been reported for type 2 diabetes (T2D). Recently, the combined effect of genetic variants has been investigated by calculating a genetic risk score. We evaluated 36 genome-wide association study (GWAS) identified SNPs in 2,679 T2D cases and 3322 controls in middle-age Han Chinese. Fourteen SNPs were significantly associated with T2D in analysis adjusted for age, sex and BMI. We calculated two genetic risk scores (GRS) (GRS1 with all the 36 SNPs and GRS2 with the 14 SNPs significantly associated with T2D). The odds ratio for T2D with each GRS point (per risk allele) …

A Digital X-Ray Tomosynthesis Coupled Near Infrared Spectral Tomography System For Dual-Modality Breast Imaging, Venkataramanan Krishnaswamy, Kelly E. Michaelsen, Brian W. Pogue, Steven P. Poplack, Ian Shaw, Ken Defrietas, Ken Brooks, Keith D. Paulsen

Dartmouth Scholarship

A Near Infrared Spectral Tomography (NIRST) system has been developed and integrated into a commercial Digital Breast Tomosynthesis (DBT) scanner to allow structural and functional imaging of breast in vivo. The NIRST instrument uses an 8-wavelength continuous wave (CW) laser-based scanning source assembly and a 75-element silicon photodiode solid-state detector panel to produce dense spectral and spatial projection data from which spectrally constrained 3D tomographic images of tissue chromophores are produced. Integration of the optical imaging system into the DBT scanner allows direct co-registration of the optical and DBT images, while also facilitating the synergistic use of x-ray contrast as …

Spatial Frequency Domain Tomography Of Protoporphyrin Ix Fluorescence In Preclinical Glioma Models, Soren D. Konecky, Chris M. Owen, Tyler Rice, Pablo A. ValdéS, Chris M. Owen, Pablo A. Valdes, David W. Roberts, Kolbein Kolste, Frederic Leblond, Keith D. Paulsen, Brian C. Wilson

Dartmouth Scholarship

Multifrequency (0 to 0.3  mm−1), multiwavelength (633, 680, 720, 800, and 820 nm) spatial frequency domain imaging (SFDI) of 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) was used to recover absorption, scattering, and fluorescence properties of glioblastoma multiforme spheroids in tissue-simulating phantoms and in vivo in a mouse model. Three-dimensional tomographic reconstructions of the frequency-dependent remitted light localized the depths of the spheroids within 500 μm, and the total amount of PpIX in the reconstructed images was constant to within 30% when spheroid depth was varied. In vivo tumor-to-normal contrast was greater than ∼ 1.5 in reduced scattering coefficient for all wavelengths …

Decision Quality Instrument For Treatment Of Hip And Knee Osteoarthritis: A Psychometric Evaluation, Karen R. Sepucha, Dawn Stacey, Catharine F. Clay, Yuchiao Chang

Dartmouth Scholarship

A high quality decision requires that patients who meet clinical criteria for surgery are informed about the options (including non-surgical alternatives) and receive treatments that match their goals. The aim of this study was to evaluate the psychometric properties and clinical sensibility of a patient self report instrument, to measure the quality of decisions about total joint replacement for knee or hip osteoarthritis.

Remote Positioning Optical Breast Magnetic Resonance Coil For Slice-Selection During Image-Guided Near-Infrared Spectroscopy Of Breast Cancer, Michael A. Mastanduno, Shudong Jiang, Brian W. Pogue, Keith D. Paulsen, Roberta Diflorio-Alexander

Dartmouth Scholarship

The design and testing of a pneumatic optical positioning interface produced with the goal of improving fiber positioning in magnetic resonance (MR)-guided diffuse spectral imaging of breast cancer is presented. The system was created for vertical positioning of optical fibers inside the MR bore during a patient exam to target suspicious lesions with MR scans for reference and collect multiple planes of optical data. The interface includes new fiber plates for mechanical and optical coupling to the breast, and was tested in phantoms and human imaging. Reconstructions with data taken in the new interface show acceptable linearity over different absorber …

Image Guided Near-Infrared Spectroscopy Of Breast Tissue In Vivo Using Boundary Element Method, Subhadra Srinivasan, Colin M. Carpenter, Hamid R. Ghadyani, Senate J. Taka, Peter A. Kaufman, Roberta M. Diflorio-Alexander, Wendy A. Wells, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

We demonstrate quantitative functional imaging using image-guided near-infrared spectroscopy (IG-NIRS) implemented with the boundary element method (BEM) for reconstructing 3-D optical property estimates in breast tissue in vivo. A multimodality MRI-NIR system was used to collect measurements of light reflectance from breast tissue. The BEM was used to model light propagation in 3-D based only on surface discretization in order to reconstruct quantitative values of total hemoglobin (HbT), oxygen saturation, water, and scatter. The technique was validated in experimental measurements from heterogeneous breast-shaped phantoms with known values and applied to a total of seven subjects comprising six healthy individuals …

Automated Classification Of Breast Pathology Using Local Measures Of Broadband Reflectance, Ashley M. Laughney, Venkataramanan Krishnaswamy, Pilar Beatriz Garcia-Allende, Olga M. Conde, Wendy A. Wells, Keith D. Paulsen, Brian W. Pogue

Dartmouth Scholarship

We demonstrate that morphological features pertinent to a tissue's pathology may be ascertained from localized measures of broadband reflectance, with a mesoscopic resolution (100-μm lateral spot size) that permits scanning of an entire margin for residual disease. The technical aspects and optimization of a k-nearest neighbor classifier for automated diagnosis of pathologies are presented, and its efficacy is validated in 29 breast tissue specimens. When discriminating between benign and malignant pathologies, a sensitivity and specificity of 91 and 77% was achieved. Furthermore, detailed subtissue-type analysis was performed to consider how diverse pathologies influence scattering response and overall classification efficacy. The …

Smart Density: A More Accurate Method Of Measuring Rural Residential Density For Health-Related Research, Peter M. Owens, Linda Titus-Ernstoff, Lucinda Gibson, Michael L. Beach, Sandy Beauregard, Madeline A. Dalton

Dartmouth Scholarship

Studies involving the built environment have typically relied on US Census data to measure residential density. However, census geographic units are often unsuited to health-related research, especially in rural areas where development is clustered and discontinuous. We evaluated the accuracy of both standard census methods and alternative GIS-based methods to measure rural density.

Development And Validation Of An Index Of Musculoskeletal Functional Limitations, Jeffrey N. Katz, Elizabeth A. Wright, John A. Baron, Elena Losina

Dartmouth Scholarship

While musculoskeletal problems are leading sources of disability, there has been little research on measuring the number of functionally limiting musculoskeletal problems for use as predictor of outcome in studies of chronic disease. This paper reports on the development and preliminary validation of a self administered musculoskeletal functional limitations index.

Noninvasive Measurement Of Aminolevulinic Acid-Induced Protoporphyrin Ix Fluorescence Allowing Detection Of Murine Glioma In Vivo, Summer L. Gibbs-Strauss, Julia A. O'Hara, P Jack Hoopes, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

Aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence is studied as a contrast agent for noninvasive detection of murine glioma, using the fluorescence-to-transmission ratio measured through the cranium. Signals measured prior to administration of ALA are very similar between control animals, 9L-GFP, and U251 tumor-bearing animals. However, 2 h after ALA administration, the PpIX signal from both tumor-bearing groups is significantly higher than the control group (9L-GFP group p-value=0.016, and U251 group p-value=0.004, relative to the control group). The variance in signal from the 9L-GFP group is much larger than either the control group or the U251 group, which is consistent …

Receiver Operating Characteristic And Location Analysis Of Simulated Near-Infrared Tomography Images, Xiaomei Song, Brian W. Pogue, Hamid Dehghani, Shudong Jiang, Keith D. Paulsen, Tor D. Tosteson

Dartmouth Scholarship

Receiver operating characteristic (ROC) analysis was performed on simulated near-infrared tomography images, using both human observer and contrast-to-noise ratio (CNR) computational assessment, for application in breast cancer imaging. In the analysis, a nonparametric approach was applied for estimating the ROC curves. Human observer detection of objects had superior capability to localize the presence of heterogeneities when the objects were small with high contrast, with a minimum detectable threshold of CNR near 3.0 to 3.3 in the images. Human observers were able to detect heterogeneities in the images below a size limit of 4 mm, yet could not accurately find the …

Near-Infrared Characterization Of Breast Tumors In Vivo Using Spectrally-Constrained Reconstruction, Subhadra Srinivasan, Brian W. Pogue, Ben Brooksby, Shudong Jiang, Hamid Dehghani, Christine Kogel, Wendy A. Wells, Steven P. Poplack, Keith D. Paulsen

Dartmouth Scholarship

Multi-wavelength Near-Infrared (NIR) Tomography was utilized in this study to non-invasively quantify physiological parameters of breast tumors using direct spectral reconstruction. Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six …

Contrast-Detail Analysis Characterizing Diffuse Optical Fluorescence Tomography Image Reconstruction, Scott C. Davis, Brian W. Pogue, Hamid Dehghani, Keith D. Paulsen

Dartmouth Scholarship

Contrast-detail analysis is used to evaluate the imaging performance of diffuse optical fluorescence tomography (DOFT), characterizing spatial resolution limits, signal-to-noise limits, and the trade-off between object contrast and size. Reconstructed images of fluorescence yield from simulated noisy data were used to determine the contrast-to-noise ratio (CNR). A threshold of CNR=3 was used to approximate a lowest acceptable noise level in the image, as a surrogate measure for human detection of objects. For objects 0.5 cm inside the edge of a simulated tissue region, the smallest diameter that met this criteria was approximately 1.7 mm, regardless of contrast level, and test …

Automated Migration Analysis Based On Cell Texture: Method & Reliability, Jianfeng Qin, Thomas W. Chittenden, Ling Gao, Justin D D. Pearlman

Dartmouth Scholarship

Background: In this paper, we present and validate a way to measure automatically the extent of cell migration based on automated examination of a series of digital photographs. It was designed specifically to identify the impact of Second Hand Smoke (SHS) on endothelial cell migration but has broader applications. The analysis has two stages: (1) preprocessing of image texture, and (2) migration analysis.

Results: The output is a graphic overlay that indicates the front lines of cell migration superimposed on each original image, with automated reporting of the distance traversed vs. time. Expert preference compares to manual placement of leading …

Improved Quantification Of Small Objects In Near-Infrared Diffuse Optical Tomography, Subhadra Srinivasan, Brian W. Pogue, Hamid Dehghani, Shudong Jiang, Xiaomei Song, Keith D. Paulsen

Dartmouth Scholarship

Diffuse optical tomography allows quantification of hemoglobin, oxygen saturation, and water in tissue, and the fidelity in this quantification is dependent on the accuracy of optical properties determined during image reconstruction. In this study, a three-step algorithm is proposed and validated that uses the standard Newton minimization with Levenberg-Marquardt regularization as the first step. The second step is a modification to the existing algorithm using a two-parameter regularization to allow lower damping in a region of interest as compared to background. This second stage allows the recovery of the actual size of an inclusion. A region-based reconstruction is the final …

Characterization Of Hemoglobin, Water, And Nir Scattering In Breast Tissue: Analysis Of Intersubject Variability And Menstrual Cycle Changes, Brian W. Pogue, Shudong Jiang, Hamid Dehghani, Christine Kogel, Sandra Soho, Subhadra Srinivasan, Xiaomei Song, Tor D. Tosteson, Steven P. Poplack, Keith D. Paulsen

Dartmouth Scholarship

Near-infrared imaging was used to quantify typical values of hemoglobin concentration, oxygen saturation, water fraction, scattering power, and scattering amplitude within the breast tissue of volunteer subjects. A systematic study of the menstrual variations in these parameters was carried out by measuring a group of seven premenopausal normal women (aged 41 to 47 years) in the follicular (days 7 to 14 of the cycle) and secretory phases (days 21 to 28) of the cycle, for two complete menstrual cycles. An average increase in hemoglobin concentration of 2.6 μM or 13% of the background breast values was observed in the …

Measuring Hospital Use Without Claims: A Comparison Of Patient And Provider Reports., R E. Clark, S K. Ricketts, G J. Mchugo

Dartmouth Scholarship

We compared the validity of hospital admission and length of stay reports from patients, outpatient providers, and hospitals, and we examined possible sources of error. Data were collected from people enrolled in a randomized trial of treatment for severe mental illness and substance use disorders, from community mental health centers (CMHCs), and from hospitals. Reports for each of the 74 study participants covered two-year time periods beginning and ending at various times between 1989 and 1993. We compared reports from the various sources and constructed a hybrid with data from all three sources. Using parametric and non-parametric statistics, we compared …