55 research outputs found
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Characterization of indeterminate breast lesions on B-mode ultrasound using automated machine learning models
Purpose: While mammography has excellent sensitivity for the detection of breast lesions, its specificity is limited. Adjunct screening with ultrasound may partially alleviate this issue, but also increases false positives, resulting in unnecessary biopsies. This study investigated the use of Google AutoML Vision (Mountain View, CA), a commercially available machine learning service, to both identify and characterize indeterminate breast lesions on ultrasound.
Methods: B-mode images from 253 independent cases of indeterminate breast lesions scheduled for core biopsy were used for model creation and validation. The performances of two sub-models from AutoML Vision, the image classification model and object detection model were evaluated, while also investigating training strategies to enhance model performances. Pathology from the patient’s biopsy were used as a reference standard.
Results: The image classification models trained under different conditions demonstrated areas under the precision recall curve (AUC) ranging from 0.85 to 0.96 during internal validation. Once deployed, the model with highest internal performance demonstrated a sensitivity of 100% (95% confidence interval (CI) of 73.5-100%), specificity of 83.3% (CI=51.6-97.9%), positive predictive value (PPV) of 85.7% (CI=62.9-95.5%), and negative predictive value (NPV) of 100% (CI non-evaluable) in an independent dataset. The object detection model demonstrated lower performance internally during development (AUC=0.67) and during prediction in the independent dataset (sensitivity=75.0% (CI=42.8-94.5), specificity=80.0% (CI=51.9-95.7), PPV=75.0% (CI=50.8-90.0), NPV=80.0% (CI=59.3-91.7%)), but was able to demonstrate the location of the lesion within the image.
Conclusions: Two models appear to be useful tools for identifying and classifying suspicious areas on B-mode images of indeterminate breast lesions
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A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran.
We report the synthesis and preliminary biologic testing of a synthetic macromolecule, (99m)Tc-diethylenetriaminepentaacetic acid (DTPA)--mannosyl-dextran, for sentinel node detection.
METHODS: Synthesis started with a 2-step process that attaches a high density of amino-terminated leashes to a dextran backbone. Allyl-bromide was reacted with pharmaceutical-grade dextran to yield allyl-dextran. After diafiltration with water, filtration, and lyophilization, the product was reacted with aminoethanethiol and ammonium persulfate. The resulting amino-conjugated dextran was dialyzed, filtered, and lyophilized. The mixed anhydride method was used to attach DTPA; after dialysis, filtration, and lyophilization, 2-imino-2-methoxyethyl-1-D-mannose was used to attach the receptor substrate. The molecular diameter was measured by dynamic light scattering. Amino, mannose, and DTPA densities were measured by trinitrobenzene sulfonate assay, sulfuric acid/phenol assay, and inductively coupled plasma spectroscopy of gadolinium-DTPA-mannosyl-dextran, respectively. Receptor affinity was measured by Scatchard assay of rabbit liver. Axillary, popliteal, and iliac lymph nodes and each injection site were assayed for radioactivity at 1 and 3 h after injection of approximately 3.7 MBq (0.050 mL) (99m)Tc-DTPA-mannosyl-dextran (0.22 nmol) or filtered (99m)Tc-sulfur colloid into the foot pads. Four animals were studied at each time point.
RESULTS: DTPA-mannosyl-dextran had a molecular weight of 35,800 g/mol and a molecular diameter of 7.1 nm. The final amine, mannose, and DTPA densities were 23, 55, and 8 mol per dextran. Labeling yields were in excess of 98% and stable for 6 h. Specific activities of 74 x 10(6) GBq/mol were achieved. The equilibrium dissociation constant for binding to the mannose-terminated glycoprotein receptor was 0.12 +/- 0.07 nmol/L. The popliteal extraction at both 1 h and 3 h was significantly (P < 0.05) higher for (99m)Tc-DTPA-mannosyl-dextran (90.1% +/- 10.7% and 97.7% +/- 2.0%, respectively) than for filtered (99m)Tc-sulfur colloid (78.8 +/- 6.5 and 67.4% +/- 26.8%, respectively). (99m)Tc-DTPA-mannosyl-dextran exhibited significantly faster injection site clearance than did filtered (99m)Tc-sulfur colloid. The (99m)Tc-DTPA-mannosyl-dextran percentage injected dose (%ID) for the front and rear paws was 52.6 +/- 10.5 and 52.3 +/- 8.0 at 1 h and 45.7 +/- 8.5 and 43.6 +/- 8.2 at 3 h after administration. The filtered (99m)Tc-sulfur colloid %ID for the front and rear paws was 70.4 +/- 11.0 and 66.3 +/- 15.1 at 1 h and 55.5 +/- 7.8 and 66.9 +/- 8.5 at 3 h. Lymph node accumulation of each agent at either 1 or 3 h was not significantly different.
CONCLUSION: (99m)Tc-DTPA-mannosyl-dextran is a receptor-based sentinel node radiotracer that exhibits the desired properties of rapid injection site clearance and low distal node accumulation. This molecule is the first member of a new class of diagnostic agents based on a macromolecular backbone with a high density of sites for the attachment of substrates and imaging reporters
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A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran.
We report the synthesis and preliminary biologic testing of a synthetic macromolecule, (99m)Tc-diethylenetriaminepentaacetic acid (DTPA)--mannosyl-dextran, for sentinel node detection.
METHODS: Synthesis started with a 2-step process that attaches a high density of amino-terminated leashes to a dextran backbone. Allyl-bromide was reacted with pharmaceutical-grade dextran to yield allyl-dextran. After diafiltration with water, filtration, and lyophilization, the product was reacted with aminoethanethiol and ammonium persulfate. The resulting amino-conjugated dextran was dialyzed, filtered, and lyophilized. The mixed anhydride method was used to attach DTPA; after dialysis, filtration, and lyophilization, 2-imino-2-methoxyethyl-1-D-mannose was used to attach the receptor substrate. The molecular diameter was measured by dynamic light scattering. Amino, mannose, and DTPA densities were measured by trinitrobenzene sulfonate assay, sulfuric acid/phenol assay, and inductively coupled plasma spectroscopy of gadolinium-DTPA-mannosyl-dextran, respectively. Receptor affinity was measured by Scatchard assay of rabbit liver. Axillary, popliteal, and iliac lymph nodes and each injection site were assayed for radioactivity at 1 and 3 h after injection of approximately 3.7 MBq (0.050 mL) (99m)Tc-DTPA-mannosyl-dextran (0.22 nmol) or filtered (99m)Tc-sulfur colloid into the foot pads. Four animals were studied at each time point.
RESULTS: DTPA-mannosyl-dextran had a molecular weight of 35,800 g/mol and a molecular diameter of 7.1 nm. The final amine, mannose, and DTPA densities were 23, 55, and 8 mol per dextran. Labeling yields were in excess of 98% and stable for 6 h. Specific activities of 74 x 10(6) GBq/mol were achieved. The equilibrium dissociation constant for binding to the mannose-terminated glycoprotein receptor was 0.12 +/- 0.07 nmol/L. The popliteal extraction at both 1 h and 3 h was significantly (P < 0.05) higher for (99m)Tc-DTPA-mannosyl-dextran (90.1% +/- 10.7% and 97.7% +/- 2.0%, respectively) than for filtered (99m)Tc-sulfur colloid (78.8 +/- 6.5 and 67.4% +/- 26.8%, respectively). (99m)Tc-DTPA-mannosyl-dextran exhibited significantly faster injection site clearance than did filtered (99m)Tc-sulfur colloid. The (99m)Tc-DTPA-mannosyl-dextran percentage injected dose (%ID) for the front and rear paws was 52.6 +/- 10.5 and 52.3 +/- 8.0 at 1 h and 45.7 +/- 8.5 and 43.6 +/- 8.2 at 3 h after administration. The filtered (99m)Tc-sulfur colloid %ID for the front and rear paws was 70.4 +/- 11.0 and 66.3 +/- 15.1 at 1 h and 55.5 +/- 7.8 and 66.9 +/- 8.5 at 3 h. Lymph node accumulation of each agent at either 1 or 3 h was not significantly different.
CONCLUSION: (99m)Tc-DTPA-mannosyl-dextran is a receptor-based sentinel node radiotracer that exhibits the desired properties of rapid injection site clearance and low distal node accumulation. This molecule is the first member of a new class of diagnostic agents based on a macromolecular backbone with a high density of sites for the attachment of substrates and imaging reporters
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Toward optimization of in vivo super‐resolution ultrasound imaging using size‐selected microbubble contrast agents
PurposeMicrovascular processes play key roles in many diseases including diabetes. Improved understanding of the microvascular changes involved in disease development could offer crucial insight into the relationship of these changes to disease pathogenesis. Super-resolution ultrasound (SR-US) imaging has showed the potential to visualize microvascular detail down to the capillary level (i.e., subwavelength resolution), but optimization is still necessary. The purpose of this study was to investigate in vivo SR-US imaging of skeletal muscle microvascularity using microbubble (MB) contrast agents of various size and concentration while evaluating different ultrasound (US) system level parameters such as imaging frame rate and image acquisition length.MethodsAn US system equipped with a linear array transducer was used in a harmonic imaging mode at low transmit power. C57BL/6J mice fed a normal diet were used in this study. An assortment of size-selected MB contrast agents (1-2 μm, 3-4 μm, and 5-8 μm in diameter) were slowly infused in the tail vein at various doses (1.25 × 107 , 2.5 × 107 , or 5 × 107 MBs). US image data were collected before MB injection and thereafter for 10 min at 30 frames per s (fps). The US transducer was fixed throughout and between each imaging period to help capture microvascular patterns along the same image plane. An adaptive SR-US image processing technique was implemented using custom Matlab software.ResultsExperimental findings illustrate the use of larger MB results in better SR-US images in terms of skeletal muscle microvascular detail. A dose of 2.5 × 107 MBs resulted in SR-US images with optimal spatial resolution. An US imaging rate of at least 20 fps and image acquisition length of at least 8 min also resulted in SR-US images with pronounced microvascular detail.ConclusionsThis study indicates that MB size and dose and US system imaging rate and data acquisition length have significant impact on the quality of in vivo SR-US images of skeletal muscle microvascularity
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