Non-invasive Quantitative Imaging Research Articles

Decreased Cerebral Perfusion in Chronic Migraine: A Voxel-based Cerebral Blood Flow Analysis Using 3D Pseudo-continuous Arterial Spin Labeling.

A contrast agent-free approach would be preferable to the frequently used invasive approaches for evaluating cerebral perfusion in chronic migraineurs (CM). In this work, non-invasive quantitative volumetric perfusion imaging was used to evaluate alterations in cerebral perfusion in CM. We used conventional brain structural imaging sequences and 3D pseudo-continuous arterial spin labeling (3D PCASL) to examine thirteen CM patients and fifteen normal controls (NCs). The entire brain gray matter underwent voxel-based analysis, and the cerebral blood flow (CBF) values of the altered positive areas were retrieved to look into the clinical variables' significant correlation. Brain regions with the decreased perfusion were located in the left postcentral gyrus, bilateral middle frontal gyrus, left middle occipital gyrus, left superior parietal lobule, left medial segment of superior frontal gyrus, and right orbital part of the inferior frontal gyrus. White matter fibers with decreased perfusion were located in bilateral superior longitudinal tracts, superior corona radiata, external capsules, anterior and posterior limbs of the internal capsule, anterior corona radiata, inferior longitudinal fasciculus, and right corticospinal tract. However, the correlation analysis showed no significant correlation between the CBF value of the above positive brain regions with clinical variables (p > 0.05). The current study provided more useful information to comprehend the pathophysiology of CM and revealed a new insight into the neural mechanism of CM from the pattern of cerebral hypoperfusion.

Diagnosis and Monitoring of Nonalcoholic Steatohepatitis: Current State and Future Directions.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease, with a worldwide prevalence of 25%. NAFLD is a spectrum that includes nonalcoholic fatty liver defined histologically by isolated hepatocytes steatosis without inflammation and nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of NAFLD and is associated with disease progression, development of cirrhosis, and increased rates of liver-specific and overall mortality. The differentiation between NAFLD and NASH as well as staging NASH are important yet challenging clinical problems. Liver biopsy is currently the standard for disease diagnosis and fibrosis staging. However, this procedure is invasive, costly, and cannot be used for longitudinal monitoring. Therefore, several noninvasive quantitative imaging biomarkers have been proposed that can estimate the severity of hepatic steatosis and fibrosis. Despite this, noninvasive diagnosis of NASH and accurate risk stratification remain unmet needs. In this work, the most relevant available imaging biomarkers are reviewed and their application in patients with NAFLD are discussed.

Evaluation of breast cancer malignancy, prognostic factors and molecular subtypes using a continuous-time random-walk MR diffusion model

PurposeTo assess the continuous-time random-walk (CTRW) model’s diagnostic value in breast lesions and to explore the associations between the CTRW parameters and breast cancer pathologic factors. MethodThis retrospective study included 85 patients (70 malignant and 18 benign lesions) who underwent 3.0T MRI examinations. Diffusion-weighted images (DWI) were acquired with 16b-values to fit the CTRW model. Three parameters (Dm, α, and β) derived from CTRW and apparent diffusion coefficient (ADC) from DWI were compared among the benign/malignant lesions, molecular prognostic factors, and molecular subtypes by Mann-Whitney U test. Spearman correlation was used to evaluate the associations between the parameters and prognostic factors. The diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC) based on the diffusion parameters. ResultsAll parameters, ADC, Dm, α, and β were significantly lower in the malignant than benign lesions (P < 0.05). The combination of all the CTRW parameters (Dm, α, and β) provided the highest AUC (0.833) and the best sensitivity (94.3%) in differentiating malignant status. And the positive status of estrogen receptor (ER) and progesterone receptor (PR) showed significantly lower β compared with the negative counterparts (P < 0.05). The high Ki-67 expression produced significantly lower Dm and ADC values (P < 0.05). Additionally, combining multiple CTRW parameters improved the performance of diagnosing molecular subtypes of breast cancer. Moreover, Spearman correlations analysis showed that β produced significant correlations with ER, PR and Ki-67 expression (P < 0.05). ConclusionsThe CTRW parameters could be used as non-invasive quantitative imaging markers to evaluate breast lesions.

Shear wave elastography evaluation of kidneys in children with familial mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder. Typical clinical manifestations are self-limiting attacks of recurrent fever, abdominal pain, arthralgia, and chest pain due to aseptic polyserositis. Renal involvement is common in FMF patients. Shear wave elastography (SWE) is a noninvasive method that provides the measurement of tissue stiffness. In this study, we aimed to show that SWE can be used as an adjunctive method for evaluating renal involvement in children with FMF. Our study group consists of 79 pediatric FMF patients and 79 control individuals. The study was planned prospectively. The variables, such as age, height, weight, and body mass index (BMI) of the patient and control groups, were kept in a similar way in order not to be affected by the differences. The right and left kidney sizes, parenchymal thicknesses, and SWE values in both groups were compared. The parenchymal stiffness degrees of the kidneys were quantified by shear modulus values in kilopascals. In our study, no statistically significant difference was found between the control and patient groups in terms of the right and left kidney longitudinal dimensions, transverse dimensions, and parenchymal thicknesses. When the kidneys were evaluated in terms of the right and left kidney stiffness values, the stiffness values in the patient group were significantly higher in both kidneys compared with those in the control group (P < 0.001). SWE can be a noninvasive quantitative imaging method that can be used to evaluate kidney involvement by detecting changes in kidney stiffness in children with FMF.

Suspicious lung lesions for malignancy: the lesion-to-spinal cord signal intensity ratio in T2WI and DWI–MRI versus PET/CT; a prospective pathologic correlated study with accuracy and ROC analyses

BackgroundThe multi-detector computed tomography (MDCT) and tissue biopsy are the gold standards for the evaluation of lung malignancies. However, there is a wide range of pulmonary indeterminate lesions that could mimic lung cancer. Furthermore, the diagnosis of malignancy could be challenging if the lesion is small and early presenting by a part-solid or ground-glass nodule or if surrounded by parenchymal lung reaction with consolidation and atelectasis. The previous literature focused on the role of diffusion-weighted image–magnetic resonance imaging (DWI) and the apparent diffusion coefficient (ADC) mapping in the evaluation of lung malignancy. A novel quantitative T2 assessment is provided and tested in this study. Aim of the work: To evaluate the accuracy of specific non-invasive quantitative magnetic resonance imaging (MRI) parameters in the characterization of suspicious lung lesions and the discrimination between the malignant and benign nature. They included the lesion-to-spinal cord signal intensity ratio in T2-WI and DWI as well as the mean and minimum apparent diffusion coefficient (ADC) values. This is performed using a prospective pathologic correlated study with receiver-operating characteristics (ROC) analysis and comparison with positron emission tomography (PET-CT) accuracy results.ResultsThis study was prospectively performed during the period between June/2021 and June/2022. It was conducted on 43 suspicious lung lesions detected by MDCT. MRI and PET/CT examinations were performed for all patients, and the results were compared to the final diagnosis obtained after biopsy and pathological assessment, using the statistical tests of significance and P-value. Cutoff values were automatically calculated, and then, accuracy tests and ROC analyses were performed. Five expert radiologists and a single consulting pulmonologist participated in this study. The inter-rater reliability ranges between good and excellent with the intra-class correlation coefficient (ICC) ranging between 0.85 and 0.94. In T2-WI: The lesion-to-spinal cord signal intensity ratio was higher in the malignant group (1.35 ± 0.29) than in the benign group (0.88 ± 0.40), (P < 0.001). At the estimated cutoff value (> 1), the sensitivity was 96.43%, the specificity was 80.00%, and AUC = 0.86. In b500-DWI: The lesion-to-spinal cord signal intensity ratio was higher in the malignant group (0.70–1.35) than in the benign group (0.20–0.70) (P < 0.001). At the estimated cutoff value (> 0.7), the sensitivity was 71.43%, the specificity was 86.67%, and AUC = 0.86. The mean and minimum ADC values were lower in the malignant group (0.6–1.3 and 0.3–1.1 × 10–3 mm2/s) than the benign group (1–1.6 and 0.7–1.4 × 10–3 mm2/s), (P < 0.01 and < 0.001, respectively). At their estimated cutoff values (≤ 1.2 and ≤ 0.9 × 10–3 mm2/s, respectively), the sensitivity was (71.4 and 85.7%), specificity was (83.3 and 66.7%), respectively, and AUC = 0.77 for both. PET/CT had 96.4% sensitivity, 92.3% specificity, and AUC = 0.94.ConclusionsPET-CT remains the most specific and sensitive tool for the differentiation between benign and malignant lesions. The lesion-to-cord signal intensity ratios in T2WI and DWI-MRI and to a minor extent the mean and minimum ADC values are also considered good parameters for this differentiation based on their accurate statistical results, particularly if PET/CT was not available or feasible. The study added to the previous literature a novel quantitative T2WI assessment which proved a high sensitivity equal to PET/CT with a lower but a good specificity. The availability, expertise, time factor, and patients' tolerance remain challenging factors for MRI.

672 Diffusion Basis Spectrum Imaging Provides Insights into Cervical Spondylotic Myelopathy Pathology

INTRODUCTION: Diffusion basis spectrum imaging (DBSI) is a non-invasive quantitative imaging modality that may improve understanding of cervical spondylotic myelopathy (CSM) pathology through detailed evaluations of spinal cord microstructural compartments. METHODS: A single-center prospective cohort study enrolled fifty CSM patients and twenty controls from 2018-2020. All patients underwent clinical evaluation and diffusion-weighted MRI, followed by diffusion tensor imaging (DTI) and DBSI analyses. Diffusion-weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. In addition, DBSI further evaluates extra-axonal changes by isotropic restricted and non-restricted fraction. Including an intra-axonal diffusion compartment, DBSI improves estimations of axonal injury via intra-axonal axial diffusivity. Patients were categorized into mild, moderate, and severe CSM using mJOA classifications. Imaging parameters were compared among patient groups using independent-samples t-tests and ANOVA. RESULTS: Twenty controls, 27 mild (mJOA 15-17), 12 moderate (12-14) and 11 severe (0-11) CSM patients were enrolled. All patient-reported outcome measures were worse in CSM patients (all p &lt; 0.001). DTI and DBSI fractional anisotropy, axial diffusivity, and radial diffusivity were significantly different between control and CSM patients (p &lt; 0.05). DBSI fiber fraction, restricted fraction, and non-restricted fraction were significantly different between groups (p &lt; 0.01). DBSI intra-axonal axial diffusivity was lower in mild compared to moderate (mean difference [95% CI]: 1.1 [0.3, 2.1], p &lt; 0.01) and severe (1.9 [1.3, 2.4], p &lt; 0.001) CSM. CONCLUSIONS: DBSI offers granular data on white matter tract integrity in CSM that provide novel insights into disease pathology, supporting its potential utility as a biomarker of CSM disease progression.

Quantification of Liver Iron Overload with MRI: Review and Guidelines from the ESGAR and SAR.

Accumulation of excess iron in the body, or systemic iron overload, results from a variety of causes. The concentration of iron in the liver is linearly related to the total body iron stores and, for this reason, quantification of liver iron concentration (LIC) is widely regarded as the best surrogate to assess total body iron. Historically assessed using biopsy, there is a clear need for noninvasive quantitative imaging biomarkers of LIC. MRI is highly sensitive to the presence of tissue iron and has been increasingly adopted as a noninvasive alternative to biopsy for detection, severity grading, and treatment monitoring in patients with known or suspected iron overload. Multiple MRI strategies have been developed in the past 2 decades, based on both gradient-echo and spin-echo imaging, including signal intensity ratio and relaxometry strategies. However, there is a general lack of consensus regarding the appropriate use of these methods. The overall goal of this article is to summarize the current state of the art in the clinical use of MRI to quantify liver iron content and to assess the overall level of evidence of these various methods. Based on this summary, expert consensus panel recommendations on best practices for MRI-based quantification of liver iron are provided.

Noninvasive Quantitative PET Imaging in Humans of the Pancreatic Beta-Cell Mass Biomarkers VMAT2 and Dopamine D2/D3 Receptors In Vivo.

Noninvasive quantitative imaging of beta-cells can provide information on changes in cellular transporters, receptors, and signaling proteins that may affect function and/or loss of mass, both of which contribute to the loss of insulin secretion and glucose regulation of patients with type 1 or type 2 diabetes (T1D/T2D). We have developed and optimized the use of two positron emission tomography (PET) radioligands, [18F]FP-(+)-DTBZ and [11C](+)-PHNO, targeting beta-cell VMAT2 and dopamine (D2/D3) receptors, respectively. Here we describe our optimized methodology for the clinical use of these two tracers for quantitative PET imaging of beta-cell biomarkers in vivo. We also briefly discuss our previous results and their implications and value towards extending the use of PET radioligand beyond the original goal of quantitative imaging of beta-cell mass to the potential to provide insight into the biology of beta-cell loss of mass and/or function and to evaluate the efficacy of therapeutics to prevent or restore functional beta-cell mass.

Diffusion Basis Spectrum Imaging Provides Insights Into Cervical Spondylotic Myelopathy Pathology.

Diffusion basis spectrum imaging (DBSI) is a noninvasive quantitative imaging modality that may improve understanding of cervical spondylotic myelopathy (CSM) pathology through detailed evaluations of spinal cord microstructural compartments. To determine the utility of DBSI as a biomarker of CSM disease severity. A single-center prospective cohort study enrolled 50 patients with CSM and 20 controls from 2018 to 2020. All patients underwent clinical evaluation and diffusion-weighted MRI, followed by diffusion tensor imaging and DBSI analyses. Diffusion-weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. In addition, DBSI further evaluates extra-axonal changes by isotropic restricted and nonrestricted fraction. Including an intra-axonal diffusion compartment, DBSI improves estimations of axonal injury through intra-axonal axial diffusivity. Patients were categorized into mild, moderate, and severe CSM using modified Japanese Orthopedic Association classifications. Imaging parameters were compared among patient groups using independent samples t tests and ANOVA. Twenty controls, 27 mild (modified Japanese Orthopedic Association 15-17), 12 moderate (12-14), and 11 severe (0-11) patients with CSM were enrolled. Diffusion tensor imaging and DBSI fractional anisotropy, axial diffusivity, and radial diffusivity were significantly different between control and patients with CSM ( P < .05). DBSI fiber fraction, restricted fraction, and nonrestricted fraction were significantly different between groups ( P < .01). DBSI intra-axonal axial diffusivity was lower in mild compared with moderate (mean difference [95% CI]: 1.1 [0.3-2.1], P < .01) and severe (1.9 [1.3-2.4], P < .001) CSM. DBSI offers granular data on white matter tract integrity in CSM that provide novel insights into disease pathology, supporting its potential utility as a biomarker of CSM disease progression.

Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects

Familial frontotemporal lobar degeneration (FTLD) is a pathologically heterogeneous group of neurodegenerative diseases with diverse genotypes and clinical phenotypes. Three major mutations were reported in patients with familial FTLD, namely, progranulin (GRN), microtubule-associated protein tau (MAPT), and the chromosome 9 open reading frame 72 (C9orf72) repeat expansion, which could cause neurodegenerative pathological changes years before symptom onset. Noninvasive quantitative molecular imaging with PET or single-photon emission CT (SPECT) allows for selective visualization of the molecular targets in vivo to investigate brain metabolism, perfusion, neuroinflammation, and pathophysiological changes. There was increasing evidence that several molecular imaging biomarkers tend to serve as biomarkers to reveal the early brain abnormalities in familial FTLD. Tau-PET with 18F-flortaucipir and 11C-PBB3 demonstrated the elevated tau position in patients with FTLD and also showed the ability to differentiate patterns among the different subtypes of the mutations in familial FTLD. Furthermore, dopamine transporter imaging with the 11C-DOPA and 11C-CFT in PET and the 123I-FP-CIT in SPECT revealed the loss of dopaminergic neurons in the asymptomatic and symptomatic patients of familial FTLD. In addition, PET imaging with the 11C-MP4A has demonstrated reduced acetylcholinesterase (AChE) activity in patients with FTLD, while PET with the 11C-DAA1106 and 11C-PK11195 revealed an increased level of microglial activation associated with neuroinflammation even before the onset of symptoms in familial FTLD. 18F-fluorodeoxyglucose (FDG)-PET indicated hypometabolism in FTLD with different mutations preceded the atrophy on MRI. Identifying molecular imaging biomarkers for familial FTLD is important for the in-vivo assessment of underlying pathophysiological changes with disease progression and future disease-modifying therapy. We review the recent progress of molecular imaging in familial FTLD with focused on the possible implication of these techniques and their prospects in specific mutation types.

A comparison study of monoexponential and fractional order calculus diffusion models and 18F-FDG PET in differentiating benign and malignant solitary pulmonary lesions and their pathological types.

ObjectiveTo evaluate the application value of monoexponential, fractional order calculus (FROC) diffusion models and PET imaging to distinguish between benign and malignant solitary pulmonary lesions (SPLs) and malignant SPLs with different pathological types and explore the correlation between each parameter and Ki67 expression.MethodsA total of 112 patients were enrolled in this study. Prior to treatment, all patients underwent a dedicated thoracic 18F-FDG PET/MR examination. Five parameters [including apparent diffusion coefficient (ADC) derived from the monoexponential model; diffusion coefficient (D), a microstructural quantity (μ), and fractional order parameter (β) derived from the FROC model and maximum standardized uptake value (SUVmax) derived from PET] were compared between benign and malignant SPLs and different pathological types of malignant SPLs. Independent sample t test, Mann-Whitney U test, DeLong test and receiver operating characteristic (ROC) curve analysis were used for statistical evaluation. Pearson correlation analysis was used to calculate the correlations between Ki-67 and ADC, D, μ, β, and SUVmax.ResultsThe ADC and D values were significantly higher and the μ and SUVmax values were significantly lower in the benign group [1.57 (1.37, 2.05) μm2/ms, 1.59 (1.52, 1.72) μm2/ms, 5.06 (3.76, 5.66) μm, 5.15 ± 2.60] than in the malignant group [1.32 (1.03, 1.51) μm2/ms, 1.43 (1.29, 1.52) μm2/ms, 7.06 (5.87, 9.45) μm, 9.85 ± 4.95]. The ADC, D and β values were significantly lower and the μ and SUVmax values were significantly higher in the squamous cell carcinoma (SCC) group [1.29 (0.66, 1.42) μm2/ms, 1.32 (1.02, 1.42) μm2/ms, 0.63 ± 0.10, 9.40 (7.76, 15.38) μm, 11.70 ± 5.98] than in the adenocarcinoma (AC) group [1.40 (1.28, 1.67) μm2/ms, 1.52 (1.44, 1.64) μm2/ms, 0.70 ± 0.10, 5.99 (4.54, 6.87) μm, 8.76 ± 4.18]. ROC curve analysis showed that for a single parameter, μ exhibited the best AUC value in discriminating between benign and malignant SPLs groups and AC and SCC groups (AUC = 0.824 and 0.911, respectively). Importantly, the combination of monoexponential, FROC models and PET imaging can further improve diagnostic performance (AUC = 0.872 and 0.922, respectively). The Pearson correlation analysis showed that Ki67 was positively correlated with μ value and negatively correlated with ADC and D values (r = 0.402, -0.346, -0.450, respectively).ConclusionThe parameters D and μ derived from the FROC model were superior to ADC and SUVmax in distinguishing benign from malignant SPLs and adenocarcinoma from squamous cell carcinoma, in addition, the combination of multiple parameters can further improve diagnostic performance. The non-Gaussian FROC diffusion model is expected to become a noninvasive quantitative imaging technique for identifying SPLs.

A Nomogram Based on Molecular Biomarkers and Radiomics to Predict Lymph Node Metastasis in Breast Cancer.

BackgroundThe aim of this study was to explore the feasibility and efficacy of a non-invasive quantitative imaging evaluation model to assess the lymphatic metastasis of breast cancer based on a radiomics signature constructed using conventional T1-weighted image (T1WI) enhanced MRI and molecular biomarkers.MethodsPatients with breast cancer diagnosed via lymph biopsies between June 2015 and June 2019 were selected for the study. All patients underwent T1WI contrast-enhancement before treatment; lymph biopsy after surgery; and simultaneous Ki-67, COX-2, PR, Her2 and proliferating cell nuclear antigen detection. All images were imported into ITK-SNAP for whole tumor delineation, and AK software was used for radiomics feature extraction. Next, the radiomics signature Rad-score was constructed after reduction of specific radiomic features. A multiple regression logistic model was built by combining the Rad-score and molecular biomarkers based on the minimum AIC.ResultsIn all, 100 patients were enrolled in this study, including 45 with non-lymph node (LN) metastasis and 55 with LN metastasis. A total of 1,051 texture feature parameters were extracted, and LASSO was used to reduce the dimensionality of the radiomics features. The log(λ) was set to 0.002786, and 19 parameters were retained for the construction of the radiomics tag Rad-score. ROC was used to evaluate the diagnostic efficiency of Rad-score: the area under the ROC curve (AUC) of the Rad-score for identifying non-lymphatic and lymphatic metastases was 0.891 in the training cohort and 0.744 in the validation cohort. With the incorporation of tumor molecular markers, the AUCs of the training cohort and validation cohort of the nomogram were 0.936 and 0.793, respectively, which were notably higher than the AUCs of the clinical parameters in the training and validation cohorts (0.719 and 0.588, respectively).ConclusionThe combined model constructed using the Rad-score and molecular biomarkers can be used as an effective non-invasive method to assess LN metastasis of breast cancer. Furthermore, it can be used to quantitatively evaluate the risk of breast cancer LN metastasis before surgery.

Correlation between diffusion kurtosis and intravoxel incoherent motion derived (IVIM) parameters and tumor tissue composition in rectal cancer: a pilot study.

To correlate non-invasive quantitative diffusion kurtosis imaging (DKI) and intravoxel incoherent motion-derived (IVIM) parameters with rectal cancer composition assessed by the expression of caudal-type homeobox 2 (CDX-2), Vimentin (VIM), CD34 and Ki-67 on resected tissues, as well as the tumor stroma ratio (TSR) and the results of H&E and Masson staining. A prospective study of 26 patients with rectal cancer who underwent magnetic resonance (MR) imaging, including DKI with 4 b values and IVIM at 3.0T prior to surgery. Primary tumor was harvested and fixed for H&E, immunohistochemistry and Masson staining. One-way ANOVA was used to test the differences. Pearson correlation coefficients and multiple linear regression analyses were applied to evaluation the correlations. The apparent diffusion coefficient (ADCDKI) and MKDKI all exhibited significant differences in subgroups with different T stages (P < 0.05) and among high- and low- grade rectal cancer (P < 0.05). MDDKI showed a moderate negative correlation with CDX-2 (r = - 0.42, P = 0.040) and a moderate positive correlation with CD34 (r = 0.42, P = 0.041). ADCIVIM exhibited a moderate positive correlation with Masson staining (r = 0.426, P = 0.048) DIVIM showed a moderate negative correlation with CDX-2 (r = - 0.58, P = 0.005). [Formula: see text] showed a moderate positive correlation with VIM (r = 0.445, P = 0.033). ADCDKI and MKDKI demonstrated a higher correlation with T stages and histologic grades. MDDKI showed significant correlations with CDX-2 and CD34. ADCIVIM showed significant correlation with Masson. DIVIM showed significant correlations with CDX-2 and [Formula: see text] showed significant correlation with VIM. These findings should be validated in a larger study.

Superficial temporal artery to middle cerebral artery bypass for flow augmentation

In the lecture to follow, we provide an in-depth review of superficial temporal artery to middle cerebral artery (STA-MCA) bypass for flow augmentation. We begin with a brief review of the two broad categories of cerebral bypasses as well and the relevant pathologies treated. We then discuss some important landmark trials on the subject of STA-MCA bypass. Next, we focus on patient selection with an emphasis on hemodynamic assessment using non-invasive quantitative imaging methods. Revascularization technique is then described with a corresponding case example and a subsequent discussion on complications and future directions.

Contrast Enhanced Ultrasound Molecular Imaging of Spontaneous Chronic Inflammatory Bowel Disease in an Interleukin-2 Receptor α-/- Transgenic Mouse Model Using Targeted Microbubbles.

Inflammatory bowel disease (IBD) is a lifelong inflammatory disorder with relapsing–remission cycles, which is currently diagnosed by clinical symptoms and signs, along with laboratory and imaging findings. However, such clinical findings are not parallel to the disease activity of IBD and are difficult to use in treatment monitoring. Therefore, non-invasive quantitative imaging tools are required for the multiple follow-up exams of IBD patients in order to monitor the disease activity and determine treatment regimens. In this study, we evaluated a dual P- and E-selectin-targeted microbubble (MBSelectin) in an interleukin-2 receptor α deficient (IL-2Rα−/−) spontaneous chronic IBD mouse model for assessing long-term anti-inflammatory effects with ultrasound molecular imaging (USMI). We used IL-2Rα−/− (male and female on a C57BL/6 genetic background; n = 39) and C57BL/6 wild-type (negative control; n = 6) mice for the study. USMI of the proximal, middle, and distal colon was performed with MBSelectin using a small animal scanner (Vevo 2100) up to six times in each IL-2Rα−/− mouse between 6–30 weeks of age. USMI signals were compared between IL-2Rα−/− vs. wild-type mice, and sexes in three colonic locations. Imaged colon segments were analyzed ex vivo for inflammatory changes on H&E-stained sections and for selectin expression by immunofluorescence staining. We successfully detected spontaneous chronic colitis in IL-2Rα−/− mice between 6–30 weeks (onset at 6–14 weeks) compared to wild-type mice. Both male and female IL-2Rα−/− mice were equally (p = 0.996) affected with the disease, and there was no significant (p > 0.05) difference in USMI signals of colitis between the proximal, middle, and distal colon. We observed the fluctuating USMI signals in IL-2Rα−/− mice between 6–30 weeks, which might suggest a resemblance of the remission-flare pattern of human IBD. The ex vivo H&E and immunostaining further confirmed the inflammatory changes, and the high expression of P- and E-selectin in the colon. The results of this study highlight the IL-2Rα−/− mice as a chronic colitis model and are suitable for the long-term assessment of treatment response using a dual P- and E-selectin-targeted USMI.

Deep-ASL enhancement technique in arterial spin labeling MRI – A novel approach for the error reduction of partial volume correction technique with linear regression algorithm

Arterial Spin Labelling MRI is a noninvasive quantitative imaging technique for measuring Cerebral Blood Flow (CBF) that plays a vital role in diagnosing different neurological disorders. Limited signal-to-noise ratio and significant partial volume effect due to the low resolution of ASL images make an accurate CBF estimation difficult. This work proposes a deep learning based ASL enhancement algorithm (Deep-ASL ENHANCE), based on the principle of single image super resolution and multi-loss joint strategy with two reconstruction modules and one weighted fusion module that employ residual dense block as the basic building block. Lack of huge amount of low quality and high quality images for training this deep learning network, is addressed by generating simulated ASL images from structural images of ADNI2. The experiment is conducted and results are evaluated on a simulated dataset in terms of different metrics such as RMSE, PSNR and SSIM. The model is also validated using clinical ASL images with the help of two independent radiologists and the results are compared using Visual Quality Score (VQS). The deep learning model trained by using simulated ASL images shows more promising results on clinical ASL data. The effectiveness of using Deep-ASL ENHANCE as a preprocessing step to the partial volume correction technique with Linear Regression algorithm (LR) has been investigated using RMSE score and it is found that CBF quantification accuracy is improved compared to the standalone LR algorithm.

Utility of shear wave ultrasound elastography in evaluation of testicular stiffness in patients with varicocele

BackgroundTesticular varicocele is the most frequent cause of male infertility. The study aimed at evaluation of testicular stiffness in patients with varicocele measured by shear wave ultrasound elastography (SWE) in correlation to patient semen analysis (total sperm count) and varicocele grade. This case–control study involved 50 patients (40 patients with bilateral testicular varicocele and 10 patients with unilateral Lt. testicular varicocele of different grades) and 25 healthy controls. All participants underwent physical examination, semen analysis (patient group subdivided in two groups: group A; normospermic and group B; oligospermic), scrotal grey scale and Doppler ultrasound, and shear wave ultrasound elastography with measurement of mean testicular stiffness. Evaluation of testicular stiffness and correlation to varicocele grade and semen analysis (total sperm count) were done.ResultsThe mean testicular stiffness value measured by SWE in patients with testicular varicocele was greater than that of healthy controls (7.46 ± 1.64 kPa vs. 3.84 ± 0.62 kPa, P < 0.001). The mean testicular stiffness value in group B exceeded that of group A (8.57 ± 1.53 kPa vs. 6.34 ± 1.76 kPa, P = 0.001). A moderate positive correlation was found between mean testicular stiffness value and the varicocele grade (P = 0.01) which was more evident in group B than in group A (P = 0.01).ConclusionsTesticular ultrasound SWE is a quantitative noninvasive imaging method which helps in the assessment of testicular parenchymal changes due to varicocele. Higher testicular stiffness values were found in testes of patients with varicocele, more in oligospermic patients than the testes of healthy controls. Testicular stiffness is moderately correlated to varicocele grade.

Preoperative assessment of microvascular invasion of hepatocellular carcinoma using non-Gaussian diffusion-weighted imaging with a fractional order calculus model: A pilot study

PurposeTo assess the clinical potential of a set of new diffusion parameters (D, β, and μ) derived from fractional order calculus (FROC) diffusion model in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Materials and methodsBetween January 2019 to November 2020, a total of 63 patients with HCC were enrolled in this study. Diffusion-weighted images were acquired by using ten b-values (0–2000 s/mm2). The FROC model parameters including diffusion coefficient (D), fractional order parameter (β), a microstructural quantity (μ) together with a conventional apparent diffusion coefficient (ADC) were calculated. Intraclass coefficients were calculated for assessing the agreement of parameters quantified by two radiologists. The differences of these values between the MVI-positive and MVI-negative HCC groups were compared by using independent sample t-test or the Mann-Whitney U test. Then the parameters showing significant differences between subgroups, including the β and D, were integrated to develop a comprehensive predictive model via binary logistic regression. The diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. ResultsAmong all the studied diffusion parameters, significant differences were found in D, β, and ADC between the MVI-positive and MVI-negative groups. MVI-positive HCCs showed significantly higher β values (0.65 ± 0.17 vs. 0.51 ± 0.13, P = 0.001), along with lower D values (0.84 ± 0.11 μm2/ms vs. 1.03 ± 0.13 μm2/ms, P < 0.001) and lower ADC values (1.38 ± 0.46 μm2/ms vs. 2.09 ± 0.70 μm2/ms, P < 0.001) than those of MVI-negative HCCs. According to the ROC analysis, the combination of D and β demonstrated the largest area under the ROC curve (0.920) compared with individual parameters (D: 0.912; β: 0.733; and ADC: 0.831) for differentiating MVI-positive from MVI-negative HCCs. ConclusionsThe FROC parameters can be used as noninvasive quantitative imaging markers for preoperatively predicting the MVI status of HCCs.

Prospective evaluation of organ-specific dose and lesional doses following therapeutic [177Lu]Lu-EDTMP administration in patients with multiple skeletal metastases and its correlation with clinical hematological toxicity.

In patients with multiple skeletal metastases, accurate estimation of absorbed doses to radiosensitive bone marrow in bone-directed systemic radionuclide therapies (RNT) is critically important from clinical dose determination standpoint. The primary aim of the present study was to estimate the radiation absorbed doses of therapeutic [177Lu]Lu-EDTMP to bone marrow by two methods viz. Medical Internal Radiation Dose (MIRD) schema and using OLINDA software and correlate with hematological toxicity. A total of 15 patients diagnosed to have multiple painful skeletal metastases being treated with [177Lu]Lu-EDTMP for palliation of pain, were enrolled for this prospective study. For all patients, urine was collected immediately after infusion of [177Lu]Lu-EDTMP up to 24 h post-administration and cumulative activity excreted from body via urine was calculated. For dosimetry, patients underwent post-administration whole-body scintigraphy at five-time points: 0.5 (pre-void), 2, 24, 48 and 120 h (post-void). From the time-activity curves generated by drawing regions of interest (ROIs) on the images, number of disintegrations was determined. Absorbed doses for organs and bone lesions were calculated using OLINDA 2.2.0 software. For bone marrow dose estimates, in addition to OLINDA 2.2.0 software, MIRD schema was also adopted. Hematological profile was monitored in all patients during the treatment and post-treatment follow-up (estimating complete blood counts, every 15 d for 3 months after therapy). The mean ± standard deviation activity of [177Lu]Lu-EDTMP administered per patient per cycle was 2.08 ± 0.45 GBq. The results demonstrated higher uptake of [177Lu]Lu-EDTMP in bone metastases compared to normal bones. Within 2 and 24 h of administration of [177Lu]Lu-EDTMP, [177Lu]Lu activity excreted from the body was 24 ± 9% and 39 ± 14%, respectively. The mean absorbed organ doses (mean ± SD) in Gy/GBq were as follows: osteogenic cells 3.15 ± 1.85, bone marrow 0.57 ± 0.31, kidneys 0.08 ± 0.05, urinary bladder 0.32 ± 0.04, and bone lesions 2.91 ± 1.88. Strong correlation was found between (a) MIRD schema and OLINDA 2.2.0 software method for estimation of bone marrow doses (r = 0.96; P = <0.0001) and (b) Bone marrow absorbed dose and hematological toxicity (r = 0.81, P = 0.0027). Radiation absorbed doses to the bone marrow and skeletal metastatic lesions, following therapeutic [177Lu]Lu-EDTMP were estimated using a convenient and non-invasive quantitative imaging method. The estimated bone marrow absorbed dose, either by MIRD schema or the OLINDA 2.2.0 software method, demonstrated strong correlation. Strong correlation was also observed between bone marrow absorbed dose and hematological toxicity.

Noninvasive Quantitative Imaging of Selective Microstructure Sizes via Magnetic Resonance

Extracting reliable and quantitative microstructure information of living tissue by non-invasive imaging is an outstanding challenge for understanding disease mechanisms and allowing early stage diagnosis of pathologies. Magnetic Resonance Imaging is the favorite technique to pursue this goal, but still provides resolution of sizes much larger than the relevant microstructure details on in-vivo studies. Monitoring molecular diffusion within tissues, is a promising mechanism to overcome the resolution limits. However, obtaining detailed microstructure information requires the acquisition of tens of images imposing long measurement times and results to be impractical for in-vivo studies. As a step towards solving this outstanding problem, we here report on a method that only requires two measurements and its proof-of-principle experiments to produce images of selective microstructure sizes by suitable dynamical control of nuclear spins with magnetic field gradients. We design microstructure-size filters with spin-echo sequences that exploit magnetization "decay-shifts" rather than the commonly used decay-rates. The outcomes of this approach are quantitative images that can be performed with current technologies, and advance towards unravelling a wealth of diagnostic information based on microstructure parameters that define the composition of biological tissues.