Tomography

Providing method descriptions that are more detailed than currently available in typical peer reviewed journals has been identified as an actionable area for improvement. In the biochemical and cell biology space, this need has been met through the creation of new journals focused on detailed protocols and materials sourcing. However, this format is not well suited for capturing instrument validation, detailed imaging protocols, and extensive statistical analysis. Furthermore, the need for additional information must be counterbalanced by the additional time burden placed upon researchers who may be already overtasked. To address these competing issues, this white paper describes protocol templates for positron emission tomography (PET), X-ray computed tomography (CT), and magnetic resonance imaging (MRI) that can be leveraged by the broad community of quantitative imaging experts to write and self-publish protocols in protocols.io. Similar to the Structured Transparent Accessible Reproducible (STAR) or Journal of Visualized Experiments (JoVE) articles, authors are encouraged to publish peer reviewed papers and then to submit more detailed experimental protocols using this template to the online resource. Such protocols should be easy to use, readily accessible, readily searchable, considered open access, enable community feedback, editable, and citable by the author. Full article

Metabolite-specific echo-planar imaging (EPI) sequences with spectral–spatial (spsp) excitation are commonly used in clinical hyperpolarized [1-¹³C]pyruvate studies because of their speed, efficiency, and flexibility. In contrast, preclinical systems typically rely on slower spectroscopic methods, such as chemical shift imaging (CSI). In this study, a 2D spspEPI sequence was developed for use on a preclinical 3T Bruker system and tested on in vivo mice experiments with patient-derived xenograft renal cell carcinoma (RCC) or prostate cancer tissues implanted in the kidney or liver. Compared to spspEPI sequences, CSI were found to have a broader point spread function via simulations and exhibited signal bleeding between vasculature and tumors in vivo. Parameters for the spspEPI sequence were optimized using simulations and verified with in vivo data. The expected lactate SNR and pharmacokinetic modeling accuracy increased with lower pyruvate flip angles (less than 15°), intermediate lactate flip angles (25° to 40°), and temporal resolution of 3 s. Overall SNR was also higher with coarser spatial resolution (4 mm isotropic vs. 2 mm isotropic). Pharmacokinetic modelling used to fit k_PL maps showed results consistent with the previous literature and across different sequences and tumor xenografts. This work describes and justifies the pulse design and parameter choices for preclinical spspEPI hyperpolarized ¹³C-pyruvate studies and shows superior image quality to CSI. Full article

This paper investigates the effect of anisotropic resolution on the image textural features of pharmacokinetic (PK) parameters of a murine glioma model using dynamic contrast-enhanced (DCE) MR images acquired with an isotropic resolution at 7T with pre-contrast T1 mapping. The PK parameter maps of whole tumors at isotropic resolution were generated using the two-compartment exchange model combined with the three-site-two-exchange model. The textural features of these isotropic images were compared with those of simulated, thick-slice, anisotropic images to assess the influence of anisotropic voxel resolution on the textural features of tumors. The isotropic images and parameter maps captured distributions of high pixel intensity that were absent in the corresponding anisotropic images with thick slices. A significant difference was observed in 33% of the histogram and textural features extracted from anisotropic images and parameter maps, compared to those extracted from corresponding isotropic images. Anisotropic images in different orthogonal orientations demonstrated 42.1% of the histogram and textural features to be significantly different from those of isotropic images. This study demonstrates that the anisotropy of voxel resolution needs to be carefully considered when comparing the textual features of tumor PK parameters and contrast-enhanced images. Full article

The purpose of this study was to evaluate whether changes in repeated lung ultrasound (LUS) or chest X-ray (CXR) of coronavirus disease 2019 (COVID-19) patients can predict the development of severe disease and the need for treatment in the intensive care unit (ICU). In this prospective monocentric study, COVID-19 patients received standardized LUS and CXR at day 1, 3 and 5. Scores for changes in LUS (LUS score) and CXR (RALE and M-RALE) were calculated and compared. Intra-class correlation was calculated for two readers of CXR and ROC analysis to evaluate the best discriminator for the need for ICU treatment. A total of 30 patients were analyzed, 26 patients with follow-up LUS and CXR. Increase in M-RALE between baseline and follow-up 1 was significantly higher in patients with need for ICU treatment in the further hospital stay (p = 0.008). Both RALE and M-RALE significantly correlated with LUS score (r = 0.5, p < 0.0001). ROC curves with need for ICU treatment as separator were not significantly different for changes in M-RALE (AUC: 0.87) and LUS score (AUC: 0.79), both being good discriminators. ICC was moderate for RALE (0.56) and substantial for M-RALE (0.74). The present study demonstrates that both follow-up LUS and CXR are powerful tools to track the evolution of COVID-19, and can be used equally as predictors for the need for ICU treatment. Full article

High Spectral and Spatial resolution (HiSS) MRI shows high diagnostic performance in the breast. Acceleration methods based on k-space undersampling could allow stronger T2*-based image contrast and/or higher spectral resolution, potentially increasing diagnostic performance. An agar/oil phantom was prepared with water-fat boundaries perpendicular to the readout and phase encoding directions in a breast coil. HiSS MRI was acquired at 3T, at sensitivity encoding (SENSE) acceleration factors R of up to 10, and the R = 1 dataset was used to simulate corresponding compressed sensing (CS) accelerations. Image quality was evaluated by quantifying noise and artifact levels. Effective spatial resolution was determined via modulation transfer function analysis. Dispersion vs. absorption (DISPA) analysis and full width at half maximum (FWHM) quantified spectral lineshape changes. Noise levels remained constant with R for CS but amplified with SENSE. SENSE preserved the spatial resolution of HiSS MRI, while CS reduced it in the phase encoding direction. SENSE showed no effect on FWHM or DISPA markers, while CS increased FWHM. Thus, CS might perform better in noise-limited or geometrically constrained applications, but in geometric configurations specific to breast MRI, spectral analysis might be compromised, decreasing the diagnostic performance of HiSS MRI. Full article

Background: Modern ultrasound (US) shear-wave dispersion (SWD) and attenuation imaging (ATI) can be used to quantify changes in the viscosity and signal attenuation of the liver parenchyma, which are altered in hepatic steatosis. We aimed to evaluate modern shear-wave elastography (SWE), SWD and ATI for the assessment of hepatic steatosis. Methods: We retrospectively analyzed the US data of 15 patients who underwent liver USs and MRIs for the evaluation of parenchymal disease/liver lesions. The USs were performed using a multifrequency convex probe (1–8 MHz). The quantitative US measurements for the SWE (m/s/kPa), the SWD (kPa-m/s/kHz) and the ATI (dB/cm/MHz) were acquired after the mean value of five regions of interest (ROIs) was calculated. The liver MRI (3T) quantification of hepatic steatosis was performed by acquiring proton density fat fraction (PDFF) mapping sequences and placing five ROIs in artifact-free areas of the PDFF scan, measuring the fat-signal fraction. We correlated the SWE, SWD and ATI measurements to the PDFF results. Results: Three patients showed mild steatosis, one showed moderate steatosis and eleven showed no steatosis in the PDFF sequences. The calculated SWE cut-off (2.5 m/s, 20.4 kPa) value identified 3/4 of patients correctly (AUC = 0.73, p > 0.05). The SWD cut-off of 18.5 m/s/kHz, which had a significant correlation (r = 0.55, p = 0.034) with the PDFF results (AUC = 0.73), identified four patients correctly (p < 0.001). The ideal ATI (AUC = 0.53 (p < 0.05)) cut-off was 0.59 dB/cm/MHz, which showed a significantly good correlation with the PDFF results (p = 0.024). Conclusion: Hepatic steatosis can be accurately detected using all the US-elastography techniques applied in this study, although the SWD and the SWE showed to be more sensitive than the PDFF. Full article

The availability of high-fidelity animal models for oncology research has grown enormously in recent years, enabling preclinical studies relevant to prevention, diagnosis, and treatment of cancer to be undertaken. This has led to increased opportunities to conduct co-clinical trials, which are studies on patients that are carried out parallel to or sequentially with animal models of cancer that mirror the biology of the patients’ tumors. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are considered to be the models that best represent human disease and have high translational value. Notably, one element of co-clinical trials that still needs significant optimization is quantitative imaging. The National Cancer Institute has organized a Co-Clinical Imaging Resource Program (CIRP) network to establish best practices for co-clinical imaging and to optimize translational quantitative imaging methodologies. This overview describes the ten co-clinical trials of investigators from eleven institutions who are currently supported by the CIRP initiative and are members of the Animal Models and Co-clinical Trials (AMCT) Working Group. Each team describes their corresponding clinical trial, type of cancer targeted, rationale for choice of animal models, therapy, and imaging modalities. The strengths and weaknesses of the co-clinical trial design and the challenges encountered are considered. The rich research resources generated by the members of the AMCT Working Group will benefit the broad research community and improve the quality and translational impact of imaging in co-clinical trials. Full article

Background: Collateral status is an important predictor for the outcome of acute ischemic stroke with large vessel occlusion. Multiphase computed-tomography angiography (mCTA) is useful to evaluate the collateral status, but visual evaluation of this examination is time-consuming. This study aims to use an artificial intelligence (AI) technique to develop an automatic AI prediction model for the collateral status of mCTA. Methods: This retrospective study enrolled subjects with acute ischemic stroke receiving endovascular thrombectomy between January 2015 and June 2020 in a tertiary referral hospital. The demographic data and images of mCTA were collected. The collateral status of all mCTA was visually evaluated. Images at the basal ganglion and supraganglion levels of mCTA were selected to produce AI models using the convolutional neural network (CNN) technique to automatically predict the collateral status of mCTA. Results: A total of 82 subjects were enrolled. There were 57 cases randomly selected for the training group and 25 cases for the validation group. In the training group, there were 40 cases with a positive collateral result (good or intermediate) and 17 cases with a negative collateral result (poor). In the validation group, there were 21 cases with a positive collateral result and 4 cases with a negative collateral result. During training for the CNN prediction model, the accuracy of the training group could reach 0.999 ± 0.015, whereas the prediction model had a performance of 0.746 ± 0.008 accuracy on the validation group. The area under the ROC curve was 0.7. Conclusions: This study suggests that the application of the AI model derived from mCTA images to automatically evaluate the collateral status is feasible. Full article

Radiation therapy (RT) is a critical part of definitive therapy for pediatric high-grade glioma (pHGG). RT is designed to treat residual tumor defined on conventional MRI (cMRI), though pHGG lesions may be ill-characterized on standard imaging. Spectroscopic MRI (sMRI) measures endogenous metabolite concentrations in the brain, and Choline (Cho)/N-acetylaspartate (NAA) ratio is a highly sensitive biomarker for metabolically active tumor. We provide a preliminary report of our study introducing a novel treatment approach of whole brain sMRI-guided proton therapy for pHGG. An observational cohort (c1 = 10 patients) receives standard of care RT; a therapeutic cohort (c2 = 15 patients) receives sMRI-guided proton RT. All patients undergo cMRI and sMRI, a high-resolution 3D whole-brain echo-planar spectroscopic imaging (EPSI) sequence (interpolated resolution of 12 µL) prior to RT and at several follow-up timepoints integrated into diagnostic scans. Treatment volumes are defined by cMRI for c1 and by cMRI and Cho/NAA ≥ 2x for c2. A longitudinal imaging database is used to quantify changes in lesion and metabolite volumes. Four subjects have been enrolled (c1 = 1/c2 = 3) with sMRI imaging follow-up of 4–18 months. Preliminary data suggest sMRI improves identification of pHGG infiltration based on abnormal metabolic activity, and using proton therapy to target sMRI-defined high-risk regions is safe and feasible. Full article

Evaluation of patient radiation dose after the implementation of a high kV technique during a cerebral angiographic procedure is an important issue. This study aimed to determine and compare the patient radiation dose of intracranial aneurysm patients undergoing cerebral angiography using the conventional and high kV techniques in a retrospective study and a phantom study. A total of 122 cases (61 cases with conventional technique and 61 cases with high kV technique) of intracranial aneurysm patients, who underwent cerebral angiographic procedure and met the inclusion criteria, were recruited. The radiation dose and the angiographic exposure parameters were reviewed retrospectively. The radiation dose in the phantom study was conducted using nanoDot^TM optically stimulating luminescence (OSLD), which were placed on the scalp of the head phantom, the back of the neck, and the phantom skin at the position of the eyes. The standard cerebral angiographic procedure using the conventional and high kV techniques was performed following the standard protocol. The results showed that the high kV technique significantly reduced patient radiation dose and phantom skin dose. This study confirms that the implementation of a high kV technique in routine cerebral angiography for aneurysm diagnosis provides an effective reduction in radiation dose. Further investigation of radiation dose in other interventional neuroradiology procedures, particularly embolization procedure, should be performed. Full article

Postoperative care of orthopedic implants is aided by imaging to assess the healing process and the implant status. MRI of implantation sites might be compromised by radiofrequency (RF) heating and RF transmission field ($B_1^{+}$) inhomogeneities induced by electrically conducting implants. This study examines the applicability of safe and $B_1^{+}$-distortion-free MRI of implantation sites using optimized parallel RF field transmission (pTx) based on a multi-objective genetic algorithm (GA). Electromagnetic field simulations were performed for eight eight-channel RF array configurations (f = 297.2 MHz), and the most efficient array was manufactured for phantom experiments at 7.0 T. Circular polarization (CP) and orthogonal projection (OP) algorithms were applied for benchmarking the GA-based shimming. $B_1^{+}$ mapping and MR thermometry and imaging were performed using phantoms mimicking muscle containing conductive implants. The local SAR10g of the entire phantom in GA was 12% and 43.8% less than the CP and OP, respectively. Experimental temperature mapping using the CP yielded ΔT = 2.5–3.0 K, whereas the GA induced no extra heating. GA-based shimming eliminated $B_1^{+}$ artefacts at implantation sites and enabled uniform gradient-echo MRI. To conclude, parallel RF transmission with GA-based excitation vectors provides a technical foundation en route to safe and $B_1^{+}$-distortion-free MRI of implantation sites. Full article

A murine model of myelofibrosis in tibia was used in a co-clinical trial to evaluate segmentation methods for application of image-based biomarkers to assess disease status. The dataset (32 mice with 157 3D MRI scans including 49 test–retest pairs scanned on consecutive days) was split into approximately 70% training, 10% validation, and 20% test subsets. Two expert annotators (EA1 and EA2) performed manual segmentations of the mouse tibia (EA1: all data; EA2: test and validation). Attention U-net (A-U-net) model performance was assessed for accuracy with respect to EA1 reference using the average Jaccard index (AJI), volume intersection ratio (AVI), volume error (AVE), and Hausdorff distance (AHD) for four training scenarios: full training, two half-splits, and a single-mouse subsets. The repeatability of computer versus expert segmentations for tibia volume of test–retest pairs was assessed by within-subject coefficient of variance (%wCV). A-U-net models trained on full and half-split training sets achieved similar average accuracy (with respect to EA1 annotations) for test set: AJI = 83–84%, AVI = 89–90%, AVE = 2–3%, and AHD = 0.5 mm–0.7 mm, exceeding EA2 accuracy: AJ = 81%, AVI = 83%, AVE = 14%, and AHD = 0.3 mm. The A-U-net model repeatability wCV [95% CI]: 3 [2, 5]% was notably better than that of expert annotators EA1: 5 [4, 9]% and EA2: 8 [6, 13]%. The developed deep learning model effectively automates murine bone marrow segmentation with accuracy comparable to human annotators and substantially improved repeatability. Full article

Orbital floor fractures represent a common fracture type of the midface and are standardly diagnosed clinically as well as radiologically using linear measurement methods. The aim of this study was to evaluate the accuracy of diagnostic measurements of isolated orbital floor fractures based on two-dimensional (2D) and three-dimensional (3D) measurement techniques. A cohort of 177 patients was retrospectively and multi-centrically evaluated after surgical treatment of an orbital floor fracture between 2010 and 2020. In addition to 2D and 3D measurements of the fracture area, further fracture-related parameters were investigated. Calculated fracture areas using the 2D measurement technique revealed an average area of 287.59 mm², whereas the 3D measurement showed fracture areas with a significantly larger average value of 374.16 mm² (p < 0.001). On average, the 3D measurements were 1.53-fold larger compared to the 2D measurements. This was observed in 145 patients, whereas only 32 patients showed smaller values in the 3D-based approach. However, the process duration of the 3D measurement took approximately twice as long as the 2D-based procedure. Nonetheless, 3D-based measurement of orbital floor defects provides a more accurate estimation of the fracture area than the 2D-based procedure and can be helpful in determining the indication and planning the surgical procedure. Full article

We have integrated a compact and lightweight PET with an existing CT image-guided small animal irradiator to enable practical onboard PET/CT image-guided preclinical radiation therapy (RT) research. The PET with a stationary and full-ring detectors has ~1.1 mm uniform spatial resolution over its imaging field-of-view of 8.0 cm diameter and 3.5 cm axial length and was mechanically installed inside the irradiator in a tandem configuration with CT and radiation unit. A common animal bed was used for acquiring sequential dual functional and anatomical images with independent PET and CT control and acquisition systems. The reconstructed dual images were co-registered based on standard multi-modality image calibration and registration processes. Phantom studies were conducted to evaluate the integrated system and dual imaging performance. The measured mean PET/CT image registration error was ~0.3 mm. With one-bed and three-bed acquisitions, initial tumor focused and whole-body [¹⁸F]FDG animal images were acquired to test the capability of onboard PET/CT image guidance for preclinical RT research. Overall, the results have shown that integrated PET/CT/RT can provide advantageous and practical onboard PET/CT image to significantly enhance the accuracy of tumor delineation and radiation targeting that should enhance the existing and enable new and potentially breakthrough preclinical RT research and applications. Full article

Quantitative MRI biomarkers are sought to replace painful and invasive sequential bone-marrow biopsies routinely used for myelofibrosis (MF) cancer monitoring and treatment assessment. Repeatability of MRI-based quantitative imaging biomarker (QIB) measurements was investigated for apparent diffusion coefficient (ADC), proton density fat fraction (PDFF), and magnetization transfer ratio (MTR) in a JAK2 V617F hematopoietic transplant model of MF. Repeatability coefficients (RCs) were determined for three defined tibia bone-marrow sections (2–9 mm; 10–12 mm; and 12.5–13.5 mm from the knee joint) across 15 diseased mice from 20–37 test-retest pairs. Scans were performed on consecutive days every two weeks for a period of 10 weeks starting 3–4 weeks after transplant. The mean RC with (95% confidence interval (CI)) for these sections, respectively, were for ADC: 0.037 (0.031, 0.050), 0.087 (0.069, 0.116), and 0.030 (0.022, 0.044) μm²/ms; for PDFF: 1.6 (1.3, 2.0), 15.5 (12.5, 20.2), and 25.5 (12.0, 33.0)%; and for MTR: 0.16 (0.14, 0.19), 0.11 (0.09, 0.15), and 0.09 (0.08, 0.15). Change-trend analysis of these QIBs identified a dynamic section within the mid-tibial bone marrow in which confident changes (exceeding RC) could be observed after a four-week interval between scans across all measured MRI-based QIBs. Our results demonstrate the capability to derive quantitative imaging metrics from mouse tibia bone marrow for monitoring significant longitudinal MF changes. Full article

The purpose of this systematic review was to analyze evidence based on existing studies on the ability of initial CT imaging to predict mortality in severe traumatic brain injuries (TBIs) in pediatric patients. An experienced librarian searched for all existing studies based on the inclusion and exclusion criteria. The studies were screened by two blinded reviewers. Of the 3277 studies included in the search, data on prevalence of imaging findings and mortality rate could only be extracted from 22 studies. A few of those studies had patient-specific data relating specific imaging findings to outcome, allowing the data analysis, calculation of the area under the curve (AUC) and receiver operating characteristic (ROC), and generation of a forest plot for each finding. The data were extracted to calculate the sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predicted value (NPV), AUC, and ROC for extradural hematoma (EDH), subdural hematoma (SDH), traumatic subarachnoid hemorrhage (tSAH), skull fractures, and edema. There were a total of 2219 patients, 747 females and 1461 males. Of the total, 564 patients died and 1651 survived; 293 patients had SDH, 76 had EDH, 347 had tSAH, 244 had skull fractures, and 416 had edema. The studies included had high bias and lower grade of evidence. Out of the different CT scan findings, brain edema had the highest SN, PPV, NPV, and AUC. EDH had the highest SP to predict in-hospital mortality. Full article

Background: The present study evaluated the cortical activation during emotional information recognition. Methods: The study group included 16 patients with depression, and 16 healthy subjects were enrolled as a control group. Patients received eight weeks of antidepressant therapy. Functional MRI evaluated the cortical activation twice in the patient group and once in the control group. The fMRI task processed the emotional information with face demonstration from the PennCNP test battery. Results: During the processing of emotional information, patients showed activation in the middle and the inferior frontal gyri, the fusiform gyrus, and the occipital cortex. After treatment, patients showed a significant decrease in the frontal cortex activation for negative face demonstration and no frontal activation for positive emotion recognition. The left superior temporal gyrus activation zone appeared in patients after treatment and in the control group. Healthy subjects showed more intense frontal cortex activation when processing neutral emotions and less when showing happy and sad faces. Activation zones in the amygdala and the insula and deactivation zones in the posterior cingulate cortex were revealed in the controls. Conclusion: This study confirms the hypothesis that anomalies in the processing of emotional stimuli can be a sign of a depressive disorder. Full article

Introduction: Termed the “silent epidemic,” traumatic brain injury (TBI) is one of the greatest global contributors not only to post-traumatic death but also to post-traumatic long-term disability. This systematic review and meta-analysis aims to specifically evaluate the prognostic value of features on initial imaging completed within 24 h of arrival in adult patients with TBI. Method: The authors followed the PRISMA 2020 checklist for systematic review and meta-analysis design and reporting. Comprehensive searches of the Medline and Embase databases were carried out. Two independent readers extracted the following demographic, clinical and imaging information using a predetermined data abstraction form. Statistics were performed using Revman 5.4.1 and R version 4.2.0. For pooled data in meta-analysis, forest plots for sensitivity and specificity were created to calculate the diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) curves were generated using a bivariate model, and diagnostic accuracy was determined using pooled sensitivity and specificity as well as the area under the receiver operator characteristic curve (AUC). Results: There were 10,733 patients over the 19 studies. Overall, most of the studies included had high levels of bias in multiple, particularly when it came to selection bias in patient sampling, bias in controlling for confounders, and reporting bias, such as in reporting missing data. Only subdural hematoma (SDH) and mortality in all TBI patients had both an AUC with 95% CI not crossing 0.5 and a DOR with 95% CI not crossing 1, at 0.593 (95% CI: 0.556–0.725) and 2.755 (95% CI: 1.474–5.148), respectively. Conclusion: In meta-analysis, only SDH with mortality in all TBI patients had a moderate but significant association. Given the small number of studies, additional research focused on initial imaging, particularly for imaging modalities other than NECT, is required in order to confirm the findings of our meta-analysis and to further evaluate the association of imaging findings and outcome. Full article