Prediction of Disease Free Survival in Laryngeal and Hypopharyngeal Cancers Using CT Perfusion and Radiomic Features: A Pilot Study
Systematic Assessment of the Impact of DTI Methodology on Fractional Anisotropy Measures in Alzheimer’s Disease

Journal Description

Tomography

Tomography (ISSN 2379-139X; ISSN 2379-1381 for printed edition) is an international, scientific, peer-reviewed open access journal on imaging technologies published quarterly online by MDPI (from Volume 7 Issue 1-2021).

Open Access— free to download, share, and reuse content. Authors receive recognition for their contribution when the paper is reused.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, and many other databases.
Rapid Publication: first decisions in 15 days; acceptance to publication in 3 days (median values for MDPI journals in the second half of 2020).
Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.

Impact Factor: 1.308 (2019)

Imprint Information Open Access

Latest Articles

Open AccessArticle

Evaluation of Amyotrophic Lateral Sclerosis-Induced Muscle Degeneration Using Magnetic Resonance-Based Relaxivity Contrast Imaging (RCI)

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Tomography 2021, 7(2), 169-179; https://doi.org/10.3390/tomography7020015 - 05 May 2021

Abstract

(1) Background: This work characterizes the sensitivity of magnetic resonance-based Relaxivity Contrast Imaging (RCI) to Amyotrophic Lateral Sclerosis (ALS)-induced changes in myofiber microstructure. Transverse Relaxivity at Tracer Equilibrium (TRATE), an RCI-based parameter, was evaluated in the lower extremities of ALS patients and healthy subjects. (2) Methods: In this IRB-approved study, 23 subjects (12 ALS patients and 11 healthy controls) were scanned at 3T (Philips, The Netherlands). RCI data were obtained during injection of a gadolinium-based contrast agent. TRATE, fat fraction and T₂ measures, were compared in five muscle groups of the calf muscle, between ALS and control populations. TRATE was also evaluated longitudinally (baseline and 6 months) and was compared to clinical measures, namely ALS Functional Rating Scale (ALSFRS-R) and Hand-Held Dynamometry (HHD), in a subset of the ALS population. (3) Results: TRATE was significantly lower (p < 0.001) in ALS-affected muscle than in healthy muscle in all muscle groups. Fat fraction differences between ALS and healthy muscle were statistically significant for the tibialis anterior (p = 0.01), tibialis posterior (p = 0.004), and peroneus longus (p = 0.02) muscle groups but were not statistically significant for the medial (p = 0.07) and lateral gastrocnemius (p = 0.06) muscles. T₂ differences between ALS and healthy muscle were statistically significant for the tibialis anterior (p = 0.004), peroneus longus (p = 0.004) and lateral gastrocnemius (p = 0.03) muscle groups but were not statistically significant for the tibialis posterior (p = 0.06) and medial gastrocnemius (p = 0.07) muscles. Longitudinally, TRATE, averaged over all patients, decreased by 28 ± 16% in the tibialis anterior, 47 ± 18% in the peroneus longus, 25 ± 19% in the tibialis posterior, 29 ± 14% in the medial gastrocnemius and 35 ± 18% in the lateral gastrocnemius muscles between two timepoints. ALSFRS-R scores were stable in two of four ALS patients. HHD scores decreased in three of four ALS patients. (4) Conclusion: RCI-based TRATE was shown to consistently differentiate ALS-affected muscle from healthy muscle and also provide a quantitative measure of longitudinal muscle degeneration. Full article

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Open AccessArticle

A Radiogenomics Ensemble to Predict EGFR and KRAS Mutations in NSCLC

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Tomography 2021, 7(2), 154-168; https://doi.org/10.3390/tomography7020014 - 29 Apr 2021

Abstract

Lung cancer causes more deaths globally than any other type of cancer. To determine the best treatment, detecting EGFR and KRAS mutations is of interest. However, non-invasive ways to obtain this information are not available. Furthermore, many times there is a lack of big enough relevant public datasets, so the performance of single classifiers is not outstanding. In this paper, an ensemble approach is applied to increase the performance of EGFR and KRAS mutation prediction using a small dataset. A new voting scheme, Selective Class Average Voting (SCAV), is proposed and its performance is assessed both for machine learning models and CNNs. For the EGFR mutation, in the machine learning approach, there was an increase in the sensitivity from 0.66 to 0.75, and an increase in AUC from 0.68 to 0.70. With the deep learning approach, an AUC of 0.846 was obtained, and with SCAV, the accuracy of the model was increased from 0.80 to 0.857. For the KRAS mutation, both in the machine learning models (0.65 to 0.71 AUC) and the deep learning models (0.739 to 0.778 AUC), a significant increase in performance was found. The results obtained in this work show how to effectively learn from small image datasets to predict EGFR and KRAS mutations, and that using ensembles with SCAV increases the performance of machine learning classifiers and CNNs. The results provide confidence that as large datasets become available, tools to augment clinical capabilities can be fielded. Full article

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Open AccessFeature PaperArticle

Whole-Body [¹⁸F]-Fluoride PET SUV Imaging to Monitor Response to Dasatinib Therapy in Castration-Resistant Prostate Cancer Bone Metastases: Secondary Results from ACRIN 6687

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Tomography 2021, 7(2), 139-153; https://doi.org/10.3390/tomography7020013 - 25 Apr 2021

Abstract

ACRIN 6687, a multi-center clinical trial evaluating differential response of bone metastases to dasatinib in men with metastatic castration-resistant prostate cancer (mCRPC), used [¹⁸F]-fluoride (NaF) PET imaging. We extend previous ACRIN 6687 dynamic imaging results by examining NaF whole-body (WB) static SUV PET scans acquired after dynamic scanning. Eighteen patients underwent WB NaF imaging prior to and 12 weeks into dasatinib treatment. Regional VOI analysis of the most NaF avid bone metastases and an automated whole-body method using Quantitative Total Bone Imaging software (QTBI; AIQ Solutions, Inc., Madison, WI, USA) were used. We assessed differences in tumor and normal bone, between pre- and on-treatment dasatinib, and evaluated parameters in association with PFS and OS. Significant decrease in average SUV_max and average SUV_peak occurred in response to dasatinib. Univariate and multivariate analysis showed NaF uptake had significant association with PFS. Pharmacodynamic changes with dasatinib in tumor bone can be identified by WB NaF PET in men with mCRPC. WB PET has the benefit of examining the entire body and is less complicated than single FOV dynamic imaging. Full article

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Open AccessArticle

The Importance of Cardiac T2* Magnetic Resonance Imaging for Monitoring Cardiac Siderosis in Thalassemia Major Patients

Narumol Chaosuwannakit

Pattarapong Makarawate

and

Chinnadol Wanitpongpun

Tomography 2021, 7(2), 130-138; https://doi.org/10.3390/tomography7020012 - 18 Apr 2021

Abstract

Objective: Cardiac T2* magnetic resonance imaging (MRI) has recently attracted considerable attention as a non-invasive method for detecting iron overload in various organs in thalassemia major patients. This study aimed to identify the prevalence of cardiac siderosis in thalassemia major patients and evaluate cardiac T2* MRI for monitoring cardiac siderosis before and after patients receive iron chelation therapy and its relation to serum ferritin, left ventricular ejection fraction, and liver iron concentration. The information gathered would be used for the direct monitoring, detection, and treatment of complications early on. Methods: A total of 119 thalassemia major patients were recruited in the present study. The cardiac T2* MRI was compared to serum ferritin levels, liver iron concentration (LIC), and left ventricular ejection fraction. All patients were classified into four groups based on their cardiac siderosis as having normal, marginal, mild to moderate, or severe cardiac iron overload. At the follow-up at years one, three, and five, the cardiac T2* MRI, LIC, serum ferritin, and left ventricular ejection fraction (LVEF) were determined. Results: The prevalence of cardiac siderosis with cardiac T2* MRI ≤ 25 ms was 17.6% (n = 21). There was no correlation between cardiac T2* MRI and serum ferritin, liver iron concentration, and LVEF (p = 0.39, 0.54, and 0.09, respectively). During one year to five years’ follow-up periods, cardiac T2* MRI (ms) in patients with severe cardiac siderosis had significantly improved from 8.5 ± 1.49 at baseline to 33.9 ± 1.9 at five years (p < 0.0001). Patients with severe, mild-moderate, marginal, and no cardiac siderosis had median LIC (mg/g dw) of 23.9 ± 6.5, 21.6 ± 13.3, 25.3 ± 7.7, and 19.9 ± 5.5 at baseline, respectively. Conclusions: This study supports the use of cardiac T2* MRI to monitor cardiac iron overload in patients who have had multiple blood transfusions. Early diagnosis and treatment of patients at risk of cardiac siderosis is a reasonable method of reducing the substantial cardiac mortality burden associated with myocardial siderosis. Cardiac T2* MRI is the best test that can identify at-risk patients who can be managed with optimization of their chelation therapy. Full article

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Open AccessArticle

CT Volumetry of Convoluted Objects—A Simple Method Using Volume Averaging

Rani Al-Senan

and

Jeffrey H. Newhouse

Tomography 2021, 7(2), 120-129; https://doi.org/10.3390/tomography7020011 - 13 Apr 2021

Abstract

Accurate measurement of object volumes using computed tomography is often important but can be challenging, especially for finely convoluted objects with severe marginal blurring from volume averaging. We aimed to test the accuracy of a simple method for volumetry by constructing, scanning and analyzing a phantom object with these characteristics which consisted of a cluster of small lucite beads embedded in petroleum jelly. Our method involves drawing simple regions of interest containing the entirety of the object and a portion of the surrounding material and using its density, along with the densities of pure lucite and petroleum jelly and the slice thickness to calculate the volume of the object in each slice. Comparison of our results with the object’s true volume showed the technique to be highly accurate, irrespective of slice thickness, image noise, reconstruction planes, spatial resolution and variations in regions of interest. We conclude that the method can be easily used for accurate volumetry in clinical and research scans without the need for specialized volumetry computer programs. Full article

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Open AccessArticle

Evaluation of the Swallow-Tail Sign and Correlations of Neuromelanin Signal with Susceptibility and Relaxations

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Tomography 2021, 7(2), 107-119; https://doi.org/10.3390/tomography7020010 - 27 Mar 2021

Abstract

The presence of a swallow-tail sign in the nigrosome-1 with hyperintense signal shown on the susceptibility-weighted imaging (SWI) has been shown to be sensitive in detecting the abnormal iron deposits in this area. A systematic evaluation in healthy subjects is required before this tool can be recommended in a widespread application. We evaluated a simple and practical SWI approach using a multiecho gradient-echo sequence with an improved contrast-to-noise ratio (CNR). We also evaluated the association of the neuromelanin imaging contrast behavior with the susceptibility and relaxation measurements. Twenty-five older and 23 young healthy adults were evaluated. The CNRs of the nigrosome-1 were compared along with method and group. Correlations of the nigrosome-1 neuromelanin signal in the neuromelanin-sensitive imaging with CNRs in the susceptibility, T1 and T2 mappings were examined. Two different coils were used to confirm the reproducibility. Compared with the single-echo, multiecho SWI can improve the CNR of the swallow-tail sign. We found significant correlations between neuromelanin signal and CNRs in the susceptibility and T2 mappings, and T1 value. The older subjects exhibited increased CNRs compared with the young adults. No significant difference was observed in the measurements between 20 and 64 channels. The multiecho technique allows the high-quality nigrosome-1 images in SWI and allows for a joint analysis of T2* and quantitative-susceptibility mapping at high spatial resolution. The correlations of neuromelanin-sensitive imaging with susceptibility and T2 imply that the iron content in the nigrosome-1 may have significant influences on the hyperintensity of neuromelanin in the magnetization transfer-related contrast. Full article

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Open AccessArticle

Assessment of Motor Dysfunction with Virtual Reality in Patients Undergoing [¹²³I]FP-CIT SPECT/CT Brain Imaging

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Tomography 2021, 7(2), 95-106; https://doi.org/10.3390/tomography7020009 - 26 Mar 2021

Abstract

[¹²³I]FP-CIT SPECT has been valuable for distinguishing Parkinson disease (PD) from essential tremor. However, its performance for quantitative assessment of motor dysfunction has not been established. A virtual reality (VR) application was developed and compared with [¹²³I]FP-CIT SPECT/CT for detection of severity of motor dysfunction. Forty-four patients (21 males, 23 females, age 64.5 ± 12.4) with abnormal [¹²³I]FP-CIT SPECT/CT underwent assessment of bradykinesia, activities of daily living, and tremor with VR. Support vector machines (SVM) machine learning models were applied to VR and SPECT data. Receiver operating characteristic (ROC) analysis demonstrated greater area under the curve (AUC) for VR (0.8418, 95% CI 0.6071–0.9617) compared with brain SPECT (0.5357, 95% CI 0.3373–0.7357, p = 0.029) for detection of motor dysfunction. Logistic regression identified VR as an independent predictor of motor dysfunction (Odds Ratio 326.4, SE 2.17, p = 0.008). SVM for prediction of the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) demonstrated greater R-squared of 0.713 (p = 0.008) for VR, compared with 0.0764 (p = 0.361) for brain SPECT. This study demonstrates that VR can be safely used in patients prior to [¹²³I]FP-CIT SPECT imaging and may improve prediction of motor dysfunction. This test has the potential to provide a simple, objective, quantitative analysis of motor symptoms in PD patients. Full article

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Open AccessReview

Dynamic Contrast Enhanced-MR CEST Urography: An Emerging Tool in the Diagnosis and Management of Upper Urinary Tract Obstruction

Shaowei Bo

Farzad Sedaghat

KowsalyaDevi Pavuluri

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Tomography 2021, 7(1), 80-94; https://doi.org/10.3390/tomography7010008 - 02 Mar 2021

Abstract

Upper urinary tract obstructions (UTOs) are blockages that inhibit the flow of urine through its normal course, leading to impaired kidney function. Imaging plays a significant role in the initial diagnosis of UTO, with anatomic imaging (primarily ultrasound (US) and non-contrast computed tomography (CT)) serving as screening tools for the detection of the dilation of the urinary collecting systems (i.e., hydronephrosis). Whether hydronephrosis represents UTO or a non-obstructive process is determined by functional imaging (typically nuclear medicine renal scintigraphy). If these exams reveal evidence of UTO but no discernable source, multiphase contrast enhanced CT urography and/or dynamic contrast enhanced MR urography (DCE-MRU) may be performed to delineate a cause. These are often performed in conjunction with direct ureteroscopic evaluation. While contrast-enhanced CT currently predominates, it can induce renal injury due to contrast induced nephropathy (CIN), subject patients to ionizing radiation and is limited in quantifying renal function (traditionally assessed by renal scintigraphy) and establishing the extent to which hydronephrosis is due to functional obstruction. Traditional MRI is similarly limited in its ability to quantify function. DCE-MRU presents concerns regarding nephrogenic systemic fibrosis (NSF), although decreased with newer gadolinium-based contrast agents, and regarding cumulative gadolinium deposition in the basal ganglia. DCE-MR CEST urography is a promising alternative, employing new MRI contrast agents and imaging schemes and allowing for concurrent assessment of renal anatomy and functional parameters. In this review we highlight clinical challenges in the diagnosis and management of UTO, identify key advances in imaging agents and techniques for DCE-MR CEST urography and provide perspective on how this technique may evolve in clinical importance. Full article

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Open AccessArticle

Respiratory Motion Mitigation and Repeatability of Two Diffusion-Weighted MRI Methods Applied to a Murine Model of Spontaneous Pancreatic Cancer

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Tomography 2021, 7(1), 66-79; https://doi.org/10.3390/tomography7010007 - 20 Feb 2021

Abstract

Respiratory motion and increased susceptibility effects at high magnetic fields pose challenges for quantitative diffusion-weighted MRI (DWI) of a mouse abdomen on preclinical MRI systems. We demonstrate the first application of radial k-space-sampled (RAD) DWI of a mouse abdomen using a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC) on a 4.7 T preclinical scanner equipped with moderate gradient capability. RAD DWI was compared with the echo-planar imaging (EPI)-based DWI method with similar voxel volumes and acquisition times over a wide range of b-values (0.64, 535, 1071, 1478, and 2141 mm²/s). The repeatability metrics are assessed in a rigorous test–retest study (n = 10 for each DWI protocol). The four-shot EPI DWI protocol leads to higher signal-to-noise ratio (SNR) in diffusion-weighted images with persisting ghosting artifacts, whereas the RAD DWI protocol produces relatively artifact-free images over all b-values examined. Despite different degrees of motion mitigation, both RAD DWI and EPI DWI allow parametric maps of apparent diffusion coefficients (ADC) to be produced, and the ADC of the PDAC tumor estimated by the two methods are 1.3 ± 0.24 and 1.5 ± 0.28 × 10⁻³ mm²/s, respectively (p = 0.075, n = 10), and those of a water phantom are 3.2 ± 0.29 and 2.8 ± 0.15 × 10⁻³ mm²/s, respectively (p = 0.001, n = 10). Bland-Altman plots and probability density function reveal good repeatability for both protocols, whose repeatability metrics do not differ significantly. In conclusion, RAD DWI enables a more effective respiratory motion mitigation but lower SNR, while the performance of EPI DWI is expected to improve with more advanced gradient hardware. Full article

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Open AccessEditorial

Publisher’s Note: Continued Publication of Tomography by MDPI

Franck Vazquez

Tomography 2021, 7(1), 65; https://doi.org/10.3390/tomography7010006 - 09 Feb 2021

Abstract

Tomography was launched in 2015 and has published international and multidisciplinary research on all aspects of imaging science, spanning from basic research to clinical trials [...] Full article

Open AccessArticle

Identifying Robust Radiomics Features for Lung Cancer by Using In-Vivo and Phantom Lung Lesions

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Tomography 2021, 7(1), 55-64; https://doi.org/10.3390/tomography7010005 - 09 Feb 2021

Abstract

We propose a novel framework for determining radiomics feature robustness by considering the effects of both biological and noise signals. This framework is preliminarily tested in a study predicting the epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC) patients. Pairs of CT images (baseline, 3-week post therapy) of 46 NSCLC patients with known EGFR mutation status were collected and a FDA-customized anthropomorphic thoracic phantom was scanned on two vendors’ scanners at four different tube currents. Delta radiomics features were extracted from the NSCLC patient CTs and reproducible, non-redundant, and informative features were identified. The feature value differences between EGFR mutant and EGFR wildtype patients were quantitatively measured as the biological signal. Similarly, radiomics features were extracted from the phantom CTs. A pairwise comparison between settings resulted in a feature value difference that was quantitatively measured as the noise signal. Biological signals were compared to noise signals at each setting to determine if the distributions were significantly different by two-sample t-test, and thus robust. Four optimal features were selected to predict EGFR mutation status, Tumor-Mass, Sigmoid-Offset-Mean, Gabor-Energy and DWT-Energy, which quantified tumor mass, tumor-parenchyma density transition at boundary, line-like pattern inside tumor and intratumoral heterogeneity, respectively. The first three variables showed robustness across the majority of studied CT acquisition parameters. The textual feature DWT-Energy was less robust. The proposed framework was able to determine robustness of radiomics features at specific settings by comparing biological signal to noise signal. Identification of robust radiomics features may improve the generalizability of radiomics models in future studies. Full article

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Open AccessArticle

A System-Agnostic, Adaptable and Extensible Animal Support Cradle System for Cardio-Respiratory-Synchronised, and Other, Multi-Modal Imaging of Small Animals

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Tomography 2021, 7(1), 39-54; https://doi.org/10.3390/tomography7010004 - 07 Feb 2021

Abstract

Standardisation of animal handling procedures for a wide range of preclinical imaging scanners will improve imaging performance and reproducibility of scientific data. Whilst there has been significant effort in defining how well scanners should operate and how in vivo experimentation should be practised, there is little detail on how to achieve optimal scanner performance with best practices in animal welfare. Here, we describe a system-agnostic, adaptable and extensible animal support cradle system for cardio-respiratory-synchronised, and other, multi-modal imaging of small animals. The animal support cradle can be adapted on a per application basis and features integrated tubing for anaesthetic and tracer delivery, an electrically driven rectal temperature maintenance system and respiratory and cardiac monitoring. Through a combination of careful material and device selection, we have described an approach that allows animals to be transferred whilst under general anaesthesia between any of the tomographic scanners we currently or have previously operated. The set-up is minimally invasive, cheap and easy to implement and for multi-modal, multi-vendor imaging of small animals. Full article

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Open AccessArticle

Systematic Assessment of the Impact of DTI Methodology on Fractional Anisotropy Measures in Alzheimer’s Disease

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Tomography 2021, 7(1), 20-38; https://doi.org/10.3390/tomography7010003 - 06 Feb 2021

Abstract

White matter microstructural changes in Alzheimer’s disease (AD) are often assessed using fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI). FA depends on the acquisition and analysis methods, including the fitting algorithm. In this study, we compared FA maps from different acquisitions and fitting algorithms in AD, mild cognitive impairment (MCI), and healthy controls (HCs) using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Three acquisitions from two vendors were compared (Siemens 30, GE 48, and Siemens 54 directions). DTI data were fit using nine fitting algorithms (four linear least squares (LLS), two weighted LLS (WLLS), and three non-linear LLS (NLLS) from four software tools (FSL, DSI-Studio, CAMINO, and AFNI). Different cluster volumes and effect-sizes were observed across acquisitions and fits, but higher consistency was observed as the number of diffusion directions increased. Significant differences were observed between HC and AD groups for all acquisitions, while significant differences between HC and MCI groups were only observed for GE48 and SI54. Using the intraclass correlation coefficient, AFNI–LLS and CAMINO–RESTORE were the least consistent with the other algorithms. By combining data across all three acquisitions and nine fits, differences between AD and HC/MCI groups were observed in the fornix and corpus callosum, indicating FA differences in these regions may be robust DTI-based biomarkers. This study demonstrates that comparisons of FA across aging populations could be confounded by variability in acquisitions and fit methodologies and that identifying the most robust DTI methodology is critical to provide more reliable DTI-based neuroimaging biomarkers for assessing microstructural changes in AD. Full article

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Open AccessArticle

Prediction of Disease Free Survival in Laryngeal and Hypopharyngeal Cancers Using CT Perfusion and Radiomic Features: A Pilot Study

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Tomography 2021, 7(1), 10-19; https://doi.org/10.3390/tomography7010002 - 05 Feb 2021

Abstract

(1) Purpose: The objective was to evaluate CT perfusion and radiomic features for prediction of one year disease free survival in laryngeal and hypopharyngeal cancer. (2) Method and Materials: This retrospective study included pre and post therapy CT neck studies in 36 patients with laryngeal/hypopharyngeal cancer. Tumor contouring was performed semi-autonomously by the computer and manually by two radiologists. Twenty-six radiomic features including morphological and gray-level features were extracted by an internally developed and validated computer-aided image analysis system. The five perfusion features analyzed included permeability surface area product (PS), blood flow (flow), blood volume (BV), mean transit time (MTT), and time-to-maximum (Tmax). One year persistent/recurrent disease data were obtained following the final treatment of definitive chemoradiation or after total laryngectomy. We performed a two-loop leave-one-out feature selection and linear discriminant analysis classifier with generation of receiver operating characteristic (ROC) curves and confidence intervals (CI). (3) Results: 10 patients (28%) had recurrence/persistent disease at 1 year. For prediction, the change in blood flow demonstrated a training AUC of 0.68 (CI 0.47–0.85) and testing AUC of 0.66 (CI 0.47–0.85). The best features selected were a combination of perfusion and radiomic features including blood flow and computer-estimated percent volume changes-training AUC of 0.68 (CI 0.5–0.85) and testing AUC of 0.69 (CI 0.5–0.85). The laryngoscopic percent change in volume was a poor predictor with a testing AUC of 0.4 (CI 0.16–0.57). (4) Conclusions: A combination of CT perfusion and radiomic features are potential predictors of one-year disease free survival in laryngeal and hypopharyngeal cancer patients. Full article

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Open AccessArticle

Design and Implementation of the Pre-Clinical DICOM Standard in Multi-Cohort Murine Studies

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Tomography 2021, 7(1), 1-9; https://doi.org/10.3390/tomography7010001 - 05 Feb 2021

Abstract

The small animal imaging Digital Imaging and Communications in Medicine (DICOM) acquisition context structured report (SR) was developed to incorporate pre-clinical data in an established DICOM format for rapid queries and comparison of clinical and non-clinical datasets. Established terminologies (i.e., anesthesia, mouse model nomenclature, veterinary definitions, NCI Metathesaurus) were utilized to assist in defining terms implemented in pre-clinical imaging and new codes were added to integrate the specific small animal procedures and handling processes, such as housing, biosafety level, and pre-imaging rodent preparation. In addition to the standard DICOM fields, the small animal SR includes fields specific to small animal imaging such as tumor graft (i.e., melanoma), tissue of origin, mouse strain, and exogenous material, including the date and site of injection. Additionally, the mapping and harmonization developed by the Mouse-Human Anatomy Project were implemented to assist co-clinical research by providing cross-reference human-to-mouse anatomies. Furthermore, since small animal imaging performs multi-mouse imaging for high throughput, and queries for co-clinical research requires a one-to-one relation, an imaging splitting routine was developed, new Unique Identifiers (UID’s) were created, and the original patient name and ID were saved for reference to the original dataset. We report the implementation of the small animal SR using MRI datasets (as an example) of patient-derived xenograft mouse models and uploaded to The Cancer Imaging Archive (TCIA) for public dissemination, and also implemented this on PET/CT datasets. The small animal SR enhancement provides researchers the ability to query any DICOM modality pre-clinical and clinical datasets using standard vocabularies and enhances co-clinical studies. Full article

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Open AccessArticle

Correlation of Tumor Hypoxia Metrics Derived from ¹⁸F-Fluoromisonidazole Positron Emission Tomography and Pimonidazole Fluorescence Images of Optically Cleared Brain Tissue

Matthew L. Scarpelli

, Debbie R. Healey, Alberto Fuentes, Vikram D. Kodibagkar and C. Chad Quarles

Tomography 2020, 6(4), 379-388; https://doi.org/10.18383/j.tom.2020.00046 - 01 Dec 2020

Abstract

¹⁸F-fluoromisonidazole (FMISO) positron emission tomography (PET) is a widely used noninvasive imaging modality for assessing hypoxia. We describe the first spatial comparison of FMISO PET with an ex vivo reference standard for hypoxia across whole tumor volumes. Eighteen rats were orthotopically implanted with C6 or 9L brain tumors and made to undergo FMISO PET scanning. Whole brains were excised, sliced into 1-mm-thick sections, optically cleared, and fluorescently imaged for pimonidazole using an in vivo imaging system. FMISO maximum tumor uptake, maximum tumor-to-cerebellar uptake (TCmax), and hypoxic fraction (extracted 110 minutes after FMISO injection) were correlated with analogous metrics derived from pimonidazole fluorescence images. FMISO SUVmax was not significantly different between C6 and 9L brain tumors (P = 0.70), whereas FMISO TCmax and hypoxic fraction were significantly greater for C6 tumors (P < 0.01). FMISO TCmax was significantly correlated with the maximum tumor pimonidazole intensity (ρ = 0.76, P < 0.01), whereas FMISO SUVmax was not. FMISO tumor hypoxic fraction was significantly correlated with the pimonidazole-derived hypoxic fraction (ρ = 0.78, P < 0.01). Given that FMISO TCmax and tumor hypoxic fraction had strong correlations with the pimonidazole reference standard, these metrics may offer more reliable measures of tumor hypoxia than conventional PET uptake metrics (SUVmax). The voxel-wise correlation between FMISO uptake and pimonidazole intensity for a given tumor was strongly dependent on the tumor’s TCmax (ρ = 0.81, P < 0.01) and hypoxic fraction (ρ = 0.85, P < 0.01), indicating PET measurements within individual voxels showed greater correlation with pimonidazole reference standard in tumors with greater hypoxia. Full article

Open AccessArticle

Evaluation of Golden-Angle-Sampled Dynamic Contrast-Enhanced MRI Reconstruction Using Objective Image Quality Measures: A Simulated Phantom Study

by Nathan Murtha, Allister Mason, Chris Bowen, Sharon Clarke, James Rioux and Steven Beyea

Tomography 2020, 6(4), 362-372; https://doi.org/10.18383/j.tom.2020.00045 - 01 Dec 2020

Abstract

We aim to extend the use of image quality metrics (IQMs) from static magnetic resonance imaging (MRI) applications to dynamic MRI studies. We assessed the use of 2 IQMs, the root mean square error and structural similarity index, in evaluating the reconstruction of quantitative dynamic contrast-enhanced (DCE) MRI data acquired using golden-angle sampling and compressed sensing (CS). To address the difficulty of obtaining ground-truth knowledge of parameters describing dynamics in real patient data, we developed a Matlab simulation framework to assess quantitative CS-DCE-MRI. We began by validating the response of each IQM to the CS-MRI reconstruction process using static data and the performance of our simulation framework with simple dynamic data. We then extended the simulations to the more realistic extended Tofts model. When assessing the Tofts model, we tested 4 different methods of selecting a reference image for the IQMs. Results from the retrospective static CS-MRI reconstructions showed that each IQM is responsive to the CS-MRI reconstruction process. Simulations of a simple contrast evolution model validated the performance of our framework. Despite the complexity of the Tofts model, both IQM scores correlated well with the recovery accuracy of a central model parameter for all reference cases studied. This finding may form the basis of algorithms for automated selection of image reconstruction aspects, such as temporal resolution, in golden-angle-sampled CS-DCE-MRI. These further suggest that objective measures of image quality may find use in general dynamic MRI applications. Full article

Open AccessPerspective

A Perspective on Cell Tracking with Magnetic Particle Imaging

Olivia C. Sehl

, Julia J. Gevaert, Kierstin P. Melo, Natasha N. Knier and Paula J. Foster

Tomography 2020, 6(4), 315-324; https://doi.org/10.18383/j.tom.2020.00043 - 01 Dec 2020

Cited by 2

Abstract

Many labs have been developing cellular magnetic resonance imaging (MRI), using both superparamagnetic iron oxide nanoparticles (SPIONs) and fluorine-19 (¹⁹F)-based cell labels, to track immune and stem cells used for cellular therapies. Although SPION-based MRI cell tracking has very high sensitivity for cell detection, SPIONs are indirectly detected owing to relaxation effects on protons, producing negative magnetic resonance contrast with low signal specificity. Therefore, it is not possible to reliably quantify the local tissue concentration of SPION particles, and cell number cannot be determined. ¹⁹F-based cell tracking has high specificity for perfluorocarbon-labeled cells, and ¹⁹F signal is directly related to cell number. However, ¹⁹F MRI has low sensitivity. Magnetic particle imaging (MPI) is a new imaging modality that directly detects SPIONs. SPION-based cell tracking using MPI displays great potential for overcoming the challenges of MRI-based cell tracking, allowing for both high cellular sensitivity and specificity, and quantification of SPION-labeled cell number. Here we describe nanoparticle and MPI system factors that influence MPI sensitivity and resolution, quantification methods, and give our perspective on testing and applying MPI for cell tracking. Full article

Open AccessArticle

Reduced Axial Scan Length Coronary Calcium Scoring Reduces Radiation Dose and Provides Adequate Clinical Decision-Making Before Coronary CT Angiography

Colin R. Young

, David A. Reynolds, Neil Gambill, Daniel I. Brooks and Todd C. Villines

Tomography 2020, 6(4), 356-361; https://doi.org/10.18383/j.tom.2020.00041 - 01 Dec 2020

Abstract

Extensive coronary artery calcium (CAC) diminishes the accuracy of coronary computed tomography angiography (CCTA). Many imagers adjust CCTA acquisition parameters depending on a preCCTA Agatston CAC score to optimize diagnostic accuracy. Typical preCCTA CAC imaging adds considerably to radiation exposure, partially attributable to imaging beyond the area known for highest CAC, the proximal coronary arteries. We aimed to determine whether a z-axis reduced scan length (RSL) would identify the majority of CAC and provide adequate information to computed tomography angiography providers relative to a standard full-scan length (FSL) preCCTA noncontrast CT. We retrospectively examined 200 subjects. The mean CAC scores detected in RSL and FSL were 77.4 (95% CI 50.6 to 104.3) and 93.9 (95% CI 57.3 to 130.5), respectively. RSL detected 81% of the FSL CAC. Among false negatives, with no CAC detected in RSL, FSL CAC severity was minimal (mean score 2.8). There was high concordance, averaging 88%, between CCTA imaging parameter adjustment decisions made by 2 experienced imagers based on either RSL or FSL. CAC detected and decision concordance decreased with increasing CAC burden. CAC detected was lower, and false negatives were more common in the right coronary artery owing to its anatomic course, placing larger segments outside RSL. Axial scan length and effective dose decreased 59% from FSL (∼14.5 cm/∼1.1 mSv) to RSL (∼5.9 cm/∼0.45 mSv). This retrospective study suggests that RSL identifies most CAC, results in similar CCTA acquisition parameter modifications, and reduces radiation exposure. Our colleagues corroborated these results in a recently published prospective study. Full article

Open AccessReview

Review of Value of CT Texture Analysis and Machine Learning in Differentiating Fat-Poor Renal Angiomyolipoma from Renal Cell Carcinoma

by Yuhan Zhang, Xu Li, Yang Lv and

Xinquan Gu

Tomography 2020, 6(4), 325-332; https://doi.org/10.18383/j.tom.2020.00039 - 01 Dec 2020

Abstract

The diagnosis of patients with suspected angiomyolipoma relies on the detection of abundant macroscopic intralesional fat, which is always of no use to differentiate fat-poor angiomyolipoma (fp-AML) from renal cell carcinoma and diagnosis of fp-AML excessively depends on individual experience. Texture analysis was proven to be a potentially useful biomarker for distinguishing between benign and malignant tumors because of its capability of providing objective and quantitative assessment of lesions by analyzing features that are not visible to the human eye. This review aimed to summarize the literature on the use of texture analysis to diagnose patients with fat-poor angiomyolipoma vs those with renal cell carcinoma and to evaluate its current application, limitations, and future challenges in order to avoid unnecessary surgical resection. Full article