Tomography

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

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

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

(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

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

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

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

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

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

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

Spatial resolution of metabolic imaging with hyperpolarized ¹³C-labeled substrates is limited owing to the multidimensional nature of spectroscopic imaging and the transient characteristics of dissolution dynamic nuclear polarization. In this study, a patch-based algorithm (PA) is proposed to enhance spatial resolution of hyperpolarized ¹³C human brain images by exploiting compartmental information from the corresponding high-resolution ¹H images. PA was validated in simulation and phantom studies. Effects of signal-to-noise ratio, upsampling factor, segmentation, and slice thickness on reconstructing ¹³C images were evaluated in simulation. PA was further applied to low-resolution human brain metabolite maps of hyperpolarized [1-¹³C] pyruvate and [1-¹³C] lactate with 3 compartment segmentations (gray matter, white matter, and cerebrospinal fluid). The performance of PA was compared with other conventional interpolation methods (sinc, nearest-neighbor, bilinear, and spline interpolations). The simulation and the phantom tests showed that PA improved spatial resolution by up to 8 times and enhanced the image contrast without compromising quantification accuracy or losing the intracompartment signal inhomogeneity, even in the case of low signal-to-noise ratio or inaccurate segmentation. PA also improved spatial resolution and image contrast of human ¹³C brain images. Dynamic analysis showed consistent performance of the proposed method even with the signal decay along time. In conclusion, PA can enhance low-resolution hyperpolarized ¹³C images in terms of spatial resolution and contrast by using a priori knowledge from high-resolution ¹H magnetic resonance imaging while preserving quantification accuracy and intracompartment signal inhomogeneity. Full article

Cognitive impairment amongst Parkinson’s disease (PD) patients is highly prevalent and associated with an increased risk of dementia. There is growing evidence that altered cerebrovascular functions contribute to cognitive impairment. Few studies have compared cerebrovascular changes in PD patients with normal and impaired cognition and those with mild-cognitive-impairment (MCI) without movement disorder. Here, we investigated arteriolar-cerebral-blood-volume (CBVa), an index reflecting the homeostasis of the most actively regulated segment in the microvasculature, using advanced MRI in various brain regions in PD and MCI patients and matched controls. Our goal is to find brain regions with altered CBVa that are specific to PD with normal and impaired cognition, and MCI-without-movement-disorder, respectively. In PD patients with normal cognition (n = 10), CBVa was significantly decreased in the substantia nigra, caudate and putamen when compared to controls. In PD patients with impaired cognition (n = 6), CBVa showed a decreasing trend in the substantia nigra, caudate and putamen, but was significantly increased in the presupplementary motor area and intracalcarine gyrus compared to controls. In MCI-patients-without-movement-disorder (n = 18), CBVa was significantly increased in the caudate, putamen, hippocampus and lingual gyrus compared to controls. These findings provide important information for efforts towards developing biomarkers for the evaluation of potential risk of PD dementia (PDD) in PD patients. The current study is limited in sample size and therefore is exploratory in nature. The data from this pilot study will serve as the basis for power analysis for subsequent studies to further investigate and validate the current findings. Full article

Radiotherapy is a common approach for the treatment of a wide variety of cancer types. Available data indicate that nanoparticles can enhance the effect of radiotherapy. We report the use of human mesenchymal stem cells to selectively deliver gold nanoparticles (GNPs) to MDA-MB-231 breast tumor xenografts in mice for the purpose of enhancing the effect of radiation therapy. Targeted delivery of GNPs to the tumor site, followed by irradiation of the tumor, enabled control of tumor growth. The results indicate that tumor-selective GNP delivery by human mesenchymal stem cells may represent a viable way to enhance the effectiveness of radiotherapy. Full article

Our institution recently implemented the use of digital tomosynthesis (DTS) to workup emergency room patients with suspected hip fractures after initial negative or indeterminate radiographs. Our purpose is to evaluate the diagnostic accuracy of DTS for hip fracture detection. We performed a retrospective review of all DTS studies over a 17-month period (July 2017 to November 2018). The results of the radiographs and DTS were recorded as either positive or negative for fracture based on the radiology report. Our reference standard for a fracture was either confirmation on subsequent CT or MRI from the same visit or documentation of clinical findings supportive of a fracture in the patient’s electronic medical record. For patients with negative DTS who did not undergo subsequent cross-sectional imaging, a missed fracture was excluded if they did not return within 30 days with a confirmed fracture. Among 91 patients, there were 34 confirmed fractures—sites including, 7 femoral necks, 10 pubic rami, and 7 greater trochanters. DTS was positive for fracture in 29 patients; 28 of these fractures were true positives, 6 confirmed on cross-sectional imaging, and 22 confirmed clinically. One false positive was observed in a patient with no clinical evidence of a fracture. Six fractures were not detected by tomosynthesis but confirmed on CT/MRI. The sensitivity and specificity of DTS are 82% and 98%, respectively, compared to that of radiographs alone at 47% and 96%, respectively. DTS is a promising adjunct to radiographs for hip fracture detection in an emergency department. Full article

Gallium-68-labeled prostate-specific membrane antigen ligands are not only established radiopharmaceuticals for staging of prostate cancer but also accumulate physiologically in nonprostate organs, including the salivary glands. We show the converted application of prostate-specific membrane antigen -positron emission tomography/computed tomography (PSMA-PET/CT) as a dedicated method to depict salivary gland tissue using a region-focused, low-dose protocol. An accessory parotid gland at the right buccal region could be confirmed; therefore, further diagnostic or invasive therapeutic steps were not necessary. Full article

Predicting biochemical recurrence of prostate cancer is imperative for initiating early treatment, which can improve the outcome of cancer treatment. However, because of inter- and intrareader variability in interpretation of F-18 fluciclovine positron emission tomography/computed tomography (PET/CT), it is difficult to reliably discern between necrotic tissue owing to radiation therapy and tumor tissue. Our goal is to develop a computational methodology using Haralick texture analysis that can be used as an adjunct tool to improve and standardize the interpretation of F-18 fluciclovine PET/CT to identify biochemical recurrence of prostate cancer. Four main textural features were chosen by variable selection procedure using least absolute shrinkage and selection operator logistic regression and bootstrapping, and then included as predictors in subsequent logistic ridge regression model for prediction (n = 28). Age at prostatectomy, prostate-specific antigen (PSA) level before the PET/CT imaging, and number of days between the prostate-specific antigen measurement and PET/CT imaging were also included in the prediction model. The overfitting-corrected area under the curve and Brier score of the proposed model were 0.94 (95% CI: 0.81, 1.00) and 0.12 (95% CI: 0.03, 0.23), respectively. Compared with a model with textural features (TI model) and that with only clinical information (CI model), the proposed model achieved 2% and 32% increase in AUC and 8% and 48% reduction in Brier score, respectively. Combining Haralick textural features based on the PET/CT imaging data with clinical information shows a high potential of enhanced prediction of the biochemical recurrence of prostate cancer. Full article

This study shows the use of hyperpolarized ¹³C magnetic resonance spectroscopic imaging (MRSI) to assess therapeutic efficacy in a preclinical tumor model. ¹³C-labeled pyruvate was used to monitor early changes in tumor metabolism based on the Warburg effect. High-grade malignant tumors exhibit increased glycolytic activity and lactate production to promote proliferation. A rodent glioma model was used to explore altered lactate production after therapy as an early imaging biomarker for therapeutic response. Rodents were surgically implanted with C6 glioma cells and separated into 4 groups, namely, no therapy, radiotherapy, chemotherapy and combined therapy. Animals were imaged serially at 6 different time points with magnetic resonance imaging at 3 T using hyperpolarized [1-¹³C]pyruvate MRSI and conventional ¹H imaging. Using hyperpolarized [1-¹³C]pyruvate MRSI, alterations in tumor metabolism were detected as changes in the conversion of lactate to pyruvate (measured as Lac/Pyr ratio) and compared with the conventional method of detecting therapeutic response using the Response Evaluation Criteria in Solid Tumors. Moreover, each therapy group expressed different characteristic changes in tumor metabolism. The group that received no therapy showed a gradual increase of Lac/Pyr ratio within the tumor. The radiotherapy group showed large variations in tumor Lac/Pyr ratio. The chemo- and combined-therapy groups showed a statistically significant reduction in tumor Lac/Pyr ratio; however, only combined therapy was capable of suppressing tumor growth, which resulted in low endpoint mortality rate. Hyperpolarized ¹³C MRSI detected a prompt reduction in Lac/Pyr ratio as early as 2 days post combined chemo- and radiotherapies. Full article

The National Institutes of Health’s (National Cancer Institute) precision medicine initiative emphasizes the biological and molecular bases for cancer prevention and treatment. Importantly, it addresses the need for consistency in preclinical and clinical research. To overcome the translational gap in cancer treatment and prevention, the cancer research community has been transitioning toward using animal models that more fatefully recapitulate human tumor biology. There is a growing need to develop best practices in translational research, including imaging research, to better inform therapeutic choices and decision-making. Therefore, the National Cancer Institute has recently launched the Co-Clinical Imaging Research Resource Program (CIRP). Its overarching mission is to advance the practice of precision medicine by establishing consensus-based best practices for co-clinical imaging research by developing optimized state-of-the-art translational quantitative imaging methodologies to enable disease detection, risk stratification, and assessment/prediction of response to therapy. In this communication, we discuss our involvement in the CIRP, detailing key considerations including animal model selection, co-clinical study design, need for standardization of co-clinical instruments, and harmonization of preclinical and clinical quantitative imaging pipelines. An underlying emphasis in the program is to develop best practices toward reproducible, repeatable, and precise quantitative imaging biomarkers for use in translational cancer imaging and therapy. We will conclude with our thoughts on informatics needs to enable collaborative and open science research to advance precision medicine. Full article