Early and late assessment of renal allograft dysfunction using intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI): a prospective study.

PURPOSE: To evaluate the ability of the Intravoxel Incoherent Motion (IVIM) and monoexponentially ADC in renal allograft function in the early and late phases of transplantation, and to predict their effectiveness in discrimination of the graft pathology. METHODS: This is a prospective study included participants scanned with quantitative diffusion and perfusion sequences on a 3-T MR scanner (Philips, Ingenia); the ADC and IVIM parameters; were calculated. Correlations and regression analysis with the eGFR, transplantation periods, and pathology were assessed. RESULTS: This study included 105 renal allograft recipients (85 males, and 20 females with mean age = 32.4 ± 11.9 years and age range = 22-61 years). There was a significant positive correlation between the whole parameters of the ADC and IVIM with eGFR however, the cortical parameters showed higher significant correlation coefficients (p < 0.001). Regression analysis revealed the most significant model can predict eGFR groups included cortical pseudo diffusion (D*) and cortical ADC (p < 0.001). In graft dysfunction eGFR was 61.5 ml/min and normal graft was 64 ml/min. This model demonstrates a high performance of an AUC 96% [0.93-0.97]. In the late transplantation, there is a higher correlation with D* compared to ADC, p-values = 0.001. CONCLUSION: IVIM and ADC Values are significant biomarkers for renal allograft function assessment, cortical ADC, and D* had the highest performance even in situations with mild impairment that is not affect the eGFR yet as cases of proteinuria with normal eGFR. Furthermore, D* is superior to ADC in the late assessment of the renal transplant.

Precise Prostate Cancer Assessment Using IVIM-Based Parametric Estimation of Blood Diffusion from DW-MRI.

Prostate cancer is a significant health concern with high mortality rates and substantial economic impact. Early detection plays a crucial role in improving patient outcomes. This study introduces a non-invasive computer-aided diagnosis (CAD) system that leverages intravoxel incoherent motion (IVIM) parameters for the detection and diagnosis of prostate cancer (PCa). IVIM imaging enables the differentiation of water molecule diffusion within capillaries and outside vessels, offering valuable insights into tumor characteristics. The proposed approach utilizes a two-step segmentation approach through the use of three U-Net architectures for extracting tumor-containing regions of interest (ROIs) from the segmented images. The performance of the CAD system is thoroughly evaluated, considering the optimal classifier and IVIM parameters for differentiation and comparing the diagnostic value of IVIM parameters with the commonly used apparent diffusion coefficient (ADC). The results demonstrate that the combination of central zone (CZ) and peripheral zone (PZ) features with the Random Forest Classifier (RFC) yields the best performance. The CAD system achieves an accuracy of 84.08% and a balanced accuracy of 82.60%. This combination showcases high sensitivity (93.24%) and reasonable specificity (71.96%), along with good precision (81.48%) and F1 score (86.96%). These findings highlight the effectiveness of the proposed CAD system in accurately segmenting and diagnosing PCa. This study represents a significant advancement in non-invasive methods for early detection and diagnosis of PCa, showcasing the potential of IVIM parameters in combination with machine learning techniques. This developed solution has the potential to revolutionize PCa diagnosis, leading to improved patient outcomes and reduced healthcare costs.

Comparison of the monoexponential and biexponential models of diffusion-weighted magnetic imaging in grading clear-cell renal cell carcinoma: a case-control study.

Background: An accurate and noninvasive method to determine the preoperative clear-cell renal cell carcinoma (ccRCC) pathological grade is of great significance for surgical program selection and prognosis assessment. Previous studies have shown that diffusion-weighted imaging (DWI) has moderate value in grading ccRCC. But DWI cannot reflect the diffusion of tissue accurately because it is calculated using a monoexponential model. Intravoxel incoherent motion (IVIM) is the biexponential model of DWI. Only a few studies have examined the value of IVIM in grading ccRCC yet with inconsistent results. This study aimed to compare the value of DWI and IVIM in grading ccRCC. Methods: In this study, 96 patients with pathologically confirmed ccRCC were evaluated by DWI and IVIM on a 3-T scanner. According to the World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification system, these patients were divided into two groups: low-grade (grade I and II) and high-grade (grade III and IV) ccRCC. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction of pseudodiffusion (f) values were calculated. The Mann-Whitney test, receiver-operating characteristic (ROC) analysis, and the Delong test were used for statistical evaluations. Results: (I) According to the WHO/ISUP nuclear grading system, 96 patients were divided into low-grade (grade I and II, 45 patients) and high-grade (grade III and IV, 51 patients) groups. (II) Compared with patients of low-grade ccRCC, the ADC and D values of those with high-grade ccRCC decreased while the D* and f values increased (P<0.05). (III) The cutoff value of the ADC, D, D*, and f in distinguishing low-grade from high-grade ccRCC was 1.50×10-3 mm2/s, 1.12×10-3 mm2/s, and 33.19×10-3 mm2/s, 0.31, respectively; the area under the curve (AUC) for the ADC, D, D*, and f values was 0.871, 0.942, 0.621, and 0.894, respectively, with the AUC of the D value being the highest; the sensitivity for the ADC, D, D*, and f values was 94.12%, 92.16%, 47.06%, and 92.16%, respectively; and the specificity for the ADC, D, D*, and f values was 66.67%, 91.11%, 77.78%, and 73.33%, respectively. (IV) Based on the Delong test, AUCD was significantly higher than AUCADC (P=0.02) and AUCD* (P<0.001), but there was no significant difference between AUCD and AUC f (P=0.18). Conclusions: Compared with the monoexponential model DWI, the biexponential model IVIM was more accurate in grading ccRCC.

The predictive value of conventional magnetic resonance imaging combined with intravoxel incoherent motion parameters for evaluating maternal and neonatal clinical outcomes in patients with placenta accreta spectrum disorders.

INTRODUCTION: We aimed to identify factors predictive of adverse maternal and neonatal outcomes in patients with placenta accreta spectrum (PAS) disorders using magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) parameters. METHOD: Fifty-six normal singleton pregnancies at 33-39 weeks of gestation underwent MRI examination at 1.5 T. The IVIM parameters were obtained from the placenta. The correlation between the f value and postpartum hemorrhage (PPH) and between the f value and transfused units of red blood cells (RBCs) was estimated by linear regression. The correlation between various influencing factors (clinical risk factors, MRI features, and IVIM parameters) and poor outcomes was investigated using univariate and multivariate analyses. RESULT: The interobserver agreement ranged from fair to excellent (k = 0.30-0.88). Multivariate analyses showed that previous cesarean sections, low signal intensity bands on T2WI and the D value were independent risk factors for adverse outcomes. The combination of three risk factors demonstrated the highest AUC of 0.903, with a sensitivity and specificity of 73.10 % and 96.90 %, respectively. Last, f was positively correlated with PPH and units of RBCs transfused. DISCUSSION: Preoperative MRI features and IVIM parameters may be used to predict poor outcomes in patients with invasive placental disorders like PAS.

Comparison of conventional diffusion-weighted imaging, diffusion kurtosis imaging and intravoxel incoherent motion in characterization of sonographically indeterminate adnexal masses.

PURPOSE: To evaluate the role of conventional diffusion weighted imaging, diffusion kurtosis imaging (DKI), and intravoxel incoherent motion (IVIM) in distinguishing benign from malignant adnexal masses. METHODS: 38 patients with 45 adnexal masses were enrolled in this prospective study and assessed with multiparametric MRI, including the IVIM-DKI sequence, on a 3 T MRI system. The mean apparent diffusion coefficient (ADC) from conventional DWI, the apparent diffusion coefficient derived from DKI (Dapp), the apparent kurtosis coefficient (Kapp), true diffusion coefficient (Dt), perfusion fraction (f) and pseudo-diffusion coefficient (Dp) were measured. RESULTS: The mean ADC, Dapp, and Dt were significantly higher in benign adnexal masses than in malignant adnexal masses (p < 0.001). f and Dp were also significantly higher in benign adnexal masses, with p values of 0.026 and 0.002, respectively. Kapp was higher in malignant masses (p < 0.001). Among mean ADC, Dapp, and Dt, mean ADC had the highest area under the curve (AUC) of 0.885. However, no statistically significant differences were observed between the ROCs of various diffusion parameters. CONCLUSION: The mean ADC, Dapp, and Kapp are useful parameters in discriminating between benign and malignant adnexal masses. Dt derived from IVIM also helps in distinguishing benign and malignant adnexal masses; however, no incremental role of IVIM and DKI over ADC could be identified in our study.

Intravoxel incoherent motion diffusion-weighted MRI for the evaluation of early spleen involvement in acute leukemia.

Background: The spleen is a frequent organ of leukemia metastasis. This study aimed to investigate the value of intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) for assessing pathologic changes in the spleen and identifying early spleen involvement in patients with acute leukemia (AL). Methods: Patients with newly diagnosed AL and healthy controls were recruited between June 2020 and November 2022. All participants underwent abdominal IVIM diffusion-weighted imaging (DWI) at our hospital. IVIM parameters [pure diffusion coefficient (D); pseudo-diffusion coefficient (D*); and pseudo-perfusion fraction (f)] of the spleen were calculated by the segmented fitting method, and perfusion-diffusion ratio (PDR) was further calculated from the values of D, D* and f. Spleen volumes (SVs) were obtained by manually segmenting the spleen layer by layer. Clinical biomarkers of AL patients were collected. Patients were divided into splenomegaly group and normal SV group according to the individualized reference intervals for SV. IVIM parameters were compared among the control group, AL with normal SV group, and AL with splenomegaly group using one-way analysis of variance, followed by pairwise post hoc comparisons. The correlations of IVIM parameters with clinical biomarkers were analyzed in AL patients. The diagnostic performances of IVIM parameters and their combinations for differentiating among the three groups were compared. Results: Seventy-nine AL patients (AL with splenomegaly: n=54; AL with normal SV: n=25) and 55 healthy controls were evaluated. IVIM parameters were significantly different among the three groups (P<0.001 for D, D* and f; P=0.001 for PDR). D and PDR showed significant differences between the control and AL with normal SV groups in pairwise comparisons (P<0.001, and P=0.031, respectively). D was correlated with white blood cell (WBC) counts (r=-0.424; 95% CI: -0.570, -0.211; P<0.001), lactate dehydrogenase (LDH) (r=-0.285; 95% CI: -0.486, -0.011; P=0.011), and bone marrow blasts (r=-0.283; 95% CI: -0.476, -0.067; P=0.012). D* (r=-0.276; 95% CI: -0.470, -0.025; P=0.014), f (r=0.514; 95% CI: 0.342, 0.664; P<0.001) and PDR (r=0.343; 95% CI: 0.208, 0.549; P=0.002) were correlated with LDH. The combination of IVIM parameters (AUC: 0.830; 95% CI: 0.729, 0.905) demonstrated better diagnostic efficacy than the single D* (AUC: 0.721; 95% CI: 0.608, 0.816; Delong test: Z=2.012, P=0.044) and f (AUC: 0.647; 95% CI: 0.532, 0.752; Delong test: Z=2.829, P=0.005), but was not significantly different from the single D (AUC: 0.756; 95% CI: 0.647, 0.846; Delong test: Z=1.676, P=0.094) in differentiating the splenomegaly group and normal SV group. Conclusions: IVIM diffusion-weighted MRI could be a potential alternative for assessing pathologic changes in the spleen from cellularity and angiogenesis, and D and PDR may be viable indicators to identify early spleen involvement in patients with AL.

Application of Intravoxel Incoherent Motion in Clinical Liver Imaging: A Literature Review.

Intravoxel incoherent motion (IVIM) modeling is a widely used double-exponential model for describing diffusion-weighted imaging (DWI) signal, with a slow component related to pure molecular diffusion and a fast component associated with microcirculatory perfusion, which compensates for the limitations of traditional DWI. IVIM is a noninvasive technique for obtaining liver pathological information and characterizing liver lesions, and has potential applications in the initial diagnosis and treatment monitoring of liver diseases. Recent studies have demonstrated that IVIM-derived parameters are useful for evaluating liver lesions, including nonalcoholic fatty liver disease (NAFLD), liver fibrosis and liver tumors. However, the results are not stable. Therefore, it is necessary to summarize the current applications of IVIM in liver disease research, identify existing shortcomings, and point out the future development direction. In this review, we searched for studies related to hepatic IVIM-DWI applications over the past two decades in the PubMed database. We first introduce the fundamental principles and influential factors of IVIM, and then discuss its application in NAFLD, liver fibrosis, and focal hepatic lesions. It has been found that IVIM is still unstable in ensuring the robustness and reproducibility of measurements in the assessment of liver fibrosis grade and liver tumors differentiation, due to inconsistent and substantial overlap in the range of IVIM-derived parameters for different fibrotic stages. In the end, the future direction of IVIM-DWI in the assessment of liver diseases is discussed, emphasizing the need for further research on the stability of IVIM-derived parameters, particularly perfusion-related parameters, in order to promote the clinical practice of IVIM-DWI. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

Quantitative tumor burden imaging parameters of the spleen at MRI for predicting treatment response in patients with acute leukemia.

Objectives: To study the value of standardized volume and intravoxel incoherent motion (IVIM) parameters of the spleen based on tumor burden for predicting treatment response in newly diagnosed acute leukemia (AL). Methods: Patients with newly diagnosed AL were recruited and underwent abdominal IVIM diffusion-weighted imaging within one week before the first induction chemotherapy. Quantitative parameters of magnetic resonance imaging (MRI) included the standardized volume (representing volumetric tumor burden) and IVIM parameters (standard apparent diffusion coefficient [sADC]; pure diffusion coefficient [D]; pseudo-diffusion coefficient [D∗]; and pseudo-perfusion fraction [f], representing functional tumor burden) of the spleen. Clinical biomarkers of tumor burden were collected. Patients were divided into complete remission (CR) and non-CR groups according to the treatment response after the first standardized induction chemotherapy, and the MRI and clinical parameters were compared between the two groups. The correlations of MRI parameters with clinical biomarkers were analyzed. Multivariate logistic regression was performed to determine the independent predictors for treatment response. Receiver operating characteristic curves were used to analyze the predicted performance. Results: 76 AL patients (CR: n = 43; non-CR: n = 33) were evaluated. Standardized spleen volume, sADC, D, f, white blood cell counts, and lactate dehydrogenase were significantly different between CR and non-CR groups (all p < 0.05). Standardized spleen volume, sADC, and D were correlated with white blood cell and lactate dehydrogenase, and f was correlated with lactate dehydrogenase (all p < 0.05). Standardized spleen volume (hazard ratio = 4.055, p = 0.042), D (hazard ratio = 0.991, p = 0.027), and f (hazard ratio = 1.142, p = 0.008) were independent predictors for treatment response, and the combination of standardized spleen volume, D, and f showed more favorable discrimination (area under the curve = 0.856) than individual predictors. Conclusion: Standardized volume, D, and f of the spleen could be used to predict treatment response in newly diagnosed AL, and the combination of morphological and functional parameters would further improve the predicted performance. IVIM parameters of the spleen may be viable indicators for evaluating functional tumor burden in AL.

Diffusion kurtosis and intravoxel incoherent motion in predicting postpartum hemorrhage in patients at high risk for placenta accreta spectrum disorders.

Background: Placenta accreta spectrum (PAS) disorder encompasses a spectrum of pathologies, from placenta accreta to placenta percreta, which is usually associated with postpartum hemorrhage (PPH). Methods: This cross-sectional study enrolled 109 patients suspected of having PAS disorders based on previous ultrasound results or clinical risk factors from November 2018 to March 2022 in Sichuan Provincial People's Hospital. Of the 109 patients, 34 had PPH and 75 did not have PPH. Magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) was performed for each patient and the apparent diffusion coefficient (ADC) from DWI, perfusion fraction (f), pure diffusion coefficient (D), and pseudo-diffusion coefficient (D*) from IVIM, and mean diffusion kurtosis (MK) and mean diffusion coefficient (MD) from DKI were measured and compared. The correlation between the DWI parameters and estimated blood loss (EBL) during surgery was identified using correlation analysis. The diagnostic performance for predicting PPH was compared between the two methods. Results: The amount of bleeding during delivery was positively correlated with D [r=0.331, P<0.001, 95% confidence interval (CI): 0.170 to 0.477], D* (r=0.389, P<0.001, 95% CI: 0.207 to 0.527), f (r=0.222, P=0.02, 95% CI: 0.036 to 0.398), and MD (r=0.277, P=0.003, 95% CI: 0.108 to 0.439), but negatively correlated with MK (r=-0.280, P=0.003, 95% CI: -0.431 to -0.098). In predicting PPH, multivariate analyses showed the independent risk factors were placenta previa and D; the area under the curve (AUC) was 0.795 (95% CI: 0.711 to 0.878) when the two risk factors were combined together. Conclusions: IVIM and DKI parameters are correlated with EBL. The combined use of placenta previa and D are helpful for predicting PPH in patients at high risk of PAS disorders.

Use of biexponential and stretched exponential models of intravoxel incoherent motion and dynamic contrast-enhanced magnetic resonance imaging to assess the proliferation of endometrial carcinoma.

Background: It is important to assess the proliferation of endometrial carcinoma (EC) noninvasively using imaging methods. This prospective diagnostic study investigated the value of biexponential and stretched exponential models of intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the Ki-67 status of EC. Methods: In all, 70 patients with EC underwent pelvic MRI. The diffusion coefficient (D), pseudo diffusion coefficient (D*), perfusion fraction (f), distributed diffusion coefficient (DDC), water molecular diffusion heterogeneity index (α), volume transfer constant (Ktrans), rate transfer constant (Kep), and volume of extravascular extracellular space per unit volume of tissue (Ve) were compared. The area under the receiver operating characteristic (ROC) curve (AUC) was used to quantify diagnostic efficacy. Multivariate logistic regression and bootstrap (1,000 samples) analyses were used to establish and evaluate, respectively, the optimal model to predict Ki-67 status. Results: D, Ktrans, and Kep were lower while α was higher in the high-proliferation group as compared with low-proliferation group (all P values<0.05). D and Kep were independent predictors of Ki-67 status in EC, and the combination of these parameters had optimal diagnostic efficacy (AUC =0.920; sensitivity 85.71%; specificity 89.29%), which was significantly better than that of D (AUC =0.753; Z=2.874; P=0.004), α (AUC =0.715; Z=3.505; P=0.001), Ktrans (AUC =0.808; Z=2.741; P=0.006), and Kep (AUC =0.832; Z=2.147; P=0.032) alone. The validation model showed good accuracy (AUC =0.882; 95% confidence interval 0.861-0.897) and consistency (C-statistic =0.902). D, Kep, Ktrans, and α showed a slightly negative (r=-0.271), moderately negative (r=-0.534), slightly negative (r=-0.409), and slightly positive (r=0.488) correlation with the Ki-67 index, respectively (all P values <0.05). Conclusions: IVIM- and DCE-MRI-derived parameters, including D, α, Ktrans, and Kep, were associated with Ki-67 status in EC, and the combination of D and Kep may serve as a superior imaging marker for the identification of low- and high-proliferation EC.

A correlative study between IVIM-DWI parameters and VEGF and MMPs expression in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Angiogenic factors may be valuable indices of tumor recurrence and treatment and potentially useful markers for predicting the response to antiangiogenesis therapy. Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are major drivers of tumor angiogenesis. Preoperatively predicting the expression of VEGF and MMPs is crucial for treating HCC. Intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) has been successfully used in the differential diagnosis of HCC, pathological grading, and treatment response evaluation. However, the correlations between IVIM-DWI parameters and VEGF and MMP expression have not been reported. This study provides a preliminary analysis of the correlation between IVIM-DWI parameters and the expression of VEGF, MMP-2, and MMP-9 to investigate the value of IVIM-DWI in the noninvasive evaluation of angiogenesis in HCC. Methods: IVIM-DWI was performed in 61 patients with HCC 1 week before they underwent surgical resection. VEGF, MMP-2, and MMP-9 expression was detected using immunohistochemistry staining. Spearman correlation analysis was used to analyze the correlations between the IVIM-DWI parameters and VEGF, MMP-2, and MMP-9 expression in HCC. Results: The fast apparent diffusion coefficient fraction (f) value was positively correlated with the expression of VEGF (P<0.001), MMP-2 (P=0.002), and MMP-9 (P<0.001). The fast apparent diffusion coefficient (D*) was positively correlated with VEGF (P<0.001) and MMP-9 (P<0.001) expression but was not correlated with MMP-2 (P=0.659) expression. The apparent diffusion coefficient (ADC) and slow apparent diffusion coefficient (D) values were not significantly correlated with the expression of VEGF (P=0.103 and P=0.543, respectively), MMP-2 (P=0.596 and P=0.338, respectively), or MMP-9 (P=0.102 and P=0.660, respectively). Conclusions: IVIM-DWI can be used to noninvasively evaluate angiogenesis in HCC.

Effects of fitting methods, high b-values and image quality on diffusion and perfusion quantification and reproducibility in the calf.

PURPOSES: The study aimed to optimize diffusion-weighted imaging (DWI) image acquisition and analysis protocols in calf muscles by investigating the effects of different model-fitting methods, image quality, and use of high b-value and constraints on parameters of interest (POIs). The optimized modeling methods were used to select the optimal combinations of b-values, which will allow shorter acquisition time while achieving the same reliability as that obtained using 16 b-values. METHODS: Test-retest baseline and high-quality DWI images of ten healthy volunteers were acquired on a 3T MR scanner, using 16 b-values, including a high b-value of 1200 s/mm2, and structural T1-weighted images for calf muscle delineation. Three and six different fitting methods were used to derive ADC from monoexponential (ME) model and Dd, fp, and Dp from intravoxel incoherent motion (IVIM) model, with or without the high b-value. The optimized ME and IVIM models were then used to determine the optimal combinations of b-values, obtainable with the least number of b-values, using the selection criteria of coefficient of variance (CV) ≤10% for all POIs. RESULTS: The find minimum multivariate algorithm was more flexible and yielded smaller fitting errors. The 2-steps fitting method, with fixed Dd, performed the best for IVIM model. The inclusion of high b-value reduced outliers, while constraints improved 2-steps fitting only. CONCLUSIONS: The optimal numbers of b-values for ME and IVIM models were nine and six b-values respectively. Test-retest reliability analyses showed that only ADC and Dd were reliable for calf diffusion evaluation, with CVs of 7.22% and 4.09%.

Utility of mono-exponential, bi-exponential, and stretched exponential signal models of intravoxel incoherent motion (IVIM) to predict prognosis and survival risk in laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) patients after chemoradiotherapy.

PURPOSE: To investigate the predictive power of mono-exponential, bi-exponential, and stretched exponential signal models of intravoxel incoherent motion (IVIM) in prognosis and survival risk of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) patients after chemoradiotherapy. MATERIALS AND METHODS: Forty-five patients with laryngeal or hypopharyngeal squamous cell carcinoma were retrospectively enrolled. All patients had undergone pretreatment IVIM examination, subsequently, mean apparent diffusion coefficient (ADCmean), maximum ADC (ADCmax), minimum ADC (ADCmin) and ADCrange (ADCmax - ADCmean) by mono-exponential model, true diffusion coefficient (D), pseudo diffusion coefficient (D*), perfusion fraction (f) by bi-exponential model, distributed diffusion coefficient (DDC), and diffusion heterogeneity index (α) by stretched exponential model were measured. Survival data were collected for 5 years. RESULTS: Thirty-one cases were in the treatment failure group and fourteen cases were in the local control group. Significantly lower ADCmean, ADCmax, ADCmin, D, f, and higher D* values were observed in the treatment failure group than in the local control group (p < 0.05). D* had the greatest AUC of 0.802, with sensitivity and specificity of 77.4 and 85.7% when D* was 38.85 × 10-3 mm2/s. Kaplan-Meier survival analysis showed that the curves of N stage, ADCmean, ADCmax, ADCmin, D, D*, f, DDC, and α values were significant. Multivariate Cox regression analysis showed ADCmean and D* were independently correlated with progression-free survival (PFS) (hazard ratio [HR] = 0.125, p = 0.001; HR = 1.008, p = 0.002, respectively). CONCLUSION: The pretreatment parameters of mono-exponential and bi-exponential models were significantly correlated with prognosis of LHSCC, ADCmean and D* values were independent factors for survival risk prediction.

Correlation between PD-L1 Expression of Non-Small Cell Lung Cancer and Data from IVIM-DWI Acquired during Magnetic Resonance of the Thorax: Preliminary Results.

This study aims to investigate the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in magnetic resonance imaging (MRI) and programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC). Twenty-one patients diagnosed with stage III NSCLC from April 2021 to April 2022 were included. The tumors were distinguished into two groups: no PD-L1 expression (<1%), and positive PD-L1 expression (≥1%). Conventional MRI and IVIM-DWI sequences were acquired with a 1.5-T system. Both fixed-size ROIs and freehand segmentations of the tumors were evaluated, and the data were analyzed through a software using four different algorithms. The diffusion (D), pseudodiffusion (D*), and perfusion fraction (pf) were obtained. The correlation between IVIM parameters and PD-L1 expression was studied with Pearson correlation coefficient. The Wilcoxon−Mann−Whitney test was used to study IVIM parameter distributions in the two groups. Twelve patients (57%) had PD-L1 ≥1%, and 9 (43%) <1%. There was a statistically significant correlation between D* values and PD-L1 expression in images analyzed with algorithm 0, for fixed-size ROIs (189.2 ± 65.709 µm²/s × 104 in no PD-L1 expression vs. 122.0 ± 31.306 µm²/s × 104 in positive PD-L1 expression, p = 0.008). The values obtained with algorithms 1, 2, and 3 were not significantly different between the groups. The IVIM-DWI MRI parameter D* can reflect PD-L1 expression in NSCLC.

Study of bone marrow microstructure in healthy young adults using intravoxel incoherent motion diffusion-weighted MRI.

Bone marrow is one of the most important organs in the human body. The evaluation of bone marrow microstructure and gender-related cellular and capillary networks in healthy young adults can help to better understand the process of bone metabolism. Intravoxel incoherent motion (IVIM) provides both diffusion and perfusion quantifications without requiring intravenous contrast agent injection. In this prospective study, 60 healthy young age-matched volunteers (30 men and 30 women) underwent MRI scans at 1.5 T using multi-b-value diffusion-weighted imaging on sagittal planes covering the lumbar bone marrow. The apparent diffusion coefficient (ADC), true ADC (D), pseudo-ADC (D*), and perfusion fraction (f) were calculated from the diffusion-weighted images using the mono- and bi-exponential models. Lumbar cancellous bone (L2-L4) was selected as the region of interest. An independent t-test was used to detect significant differences in ADC values and IVIM parameters between men and women. The differences in IVIM parameters among the L2, L3, and L4 groups were compared with analysis of variance. The D and f values in women were significantly higher than that in men (p = 0.001, 0.026). However, D* was significantly lower in women than that in men (p = 0.001). Furthermore, there was no significant gender difference for the conventional ADC value (p = 0.186). Moreover, there were no significant differences in the D, f, and D* values among the L2, L3, and L4 vertebras of women or men. IVIM parameters can show differences in bone marrow between young women and men. As a non-invasive method, it can assess bone marrow microstructure, such as cellularity and perfusion.

Self-supervised neural network improves tri-exponential intravoxel incoherent motion model fitting compared to least-squares fitting in non-alcoholic fatty liver disease.

Recent literature suggests that tri-exponential models may provide additional information and fit liver intravoxel incoherent motion (IVIM) data more accurately than conventional bi-exponential models. However, voxel-wise fitting of IVIM results in noisy and unreliable parameter maps. For bi-exponential IVIM, neural networks (NN) were able to produce superior parameter maps than conventional least-squares (LSQ) generated images. Hence, to improve parameter map quality of tri-exponential IVIM, we developed an unsupervised physics-informed deep neural network (IVIM3-NET). We assessed its performance in simulations and in patients with non-alcoholic fatty liver disease (NAFLD) and compared outcomes with bi-exponential LSQ and NN fits and tri-exponential LSQ fits. Scanning was performed using a 3.0T free-breathing multi-slice diffusion-weighted single-shot echo-planar imaging sequence with 18 b-values. Images were analysed for visual quality, comparing the bi- and tri-exponential IVIM models for LSQ fits and NN fits using parameter-map signal-to-noise ratios (SNR) and adjusted R 2. IVIM parameters were compared to histological fibrosis, disease activity and steatosis grades. Parameter map quality improved with bi- and tri-exponential NN approaches, with a significant increase in average parameter-map SNR from 3.38 to 5.59 and 2.45 to 4.01 for bi- and tri-exponential LSQ and NN models respectively. In 33 out of 36 patients, the tri-exponential model exhibited higher adjusted R 2 values than the bi-exponential model. Correlating IVIM data to liver histology showed that the bi- and tri-exponential NN outperformed both LSQ models for the majority of IVIM parameters (10 out of 15 significant correlations). Overall, our results support the use of a tri-exponential IVIM model in NAFLD. We show that the IVIM3-NET can be used to improve image quality compared to a tri-exponential LSQ fit and provides promising correlations with histopathology similar to the bi-exponential neural network fit, while generating potentially complementary additional parameters.

Sensitivity and specificity of amide proton transfer-weighted imaging for assessing programmed death-ligand 1 status in non-small cell lung cancer: a comparative study with intravoxel incoherent motion and 18F-FDG PET.

Background: Noninvasive assessment of programmed death-ligand 1 (PD-L1) expression status in non-small cell lung cancer (NSCLC) is necessary. This study arm to investigate the value of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET), diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and amide proton transfer-weighted imaging (APTWI) in the assessment of PD-L1 status in NSCLC. Methods: This is a prospective diagnostic study. A total of 76 patients with NSCLC underwent chest 18F-FDG PET/magnetic resonance imaging (MRI). Parameters maximum standardized uptake value (SUVmax), quantitate the metabolic tumor volume (MTV), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f), and magnetization transfer ratio asymmetry at 3.5 ppm [MTRasym (3.5 ppm)] from 18F-FDG PET, DWI, IVIM, and APTWI, respectively, were compared. The optimal combination of parameters was investigated using logistic regression models and evaluated by area under the receiver operating characteristic (ROC) curve (AUC). The bootstrap with 1,000 samples was used for model validation. Results: SUVmax, MTV, TLG, and MTRasym (3.5 ppm) were higher and D and f were lower in PD-L1 positive NSCLC than in PD-L1 negative NSCLC (all P<0.05). Logistic analysis showed that the combination of MTRasym (3.5 ppm), D, and SUVmax had the strongest predictive value for the differentiation of PD-L1 positive and PD-L1 negative NSCLC [AUC, 0.946; 95% confidence interval (CI): 0.869-0.985; sensitivity, 85.29%; specificity, 91.67%; P all <0.001]. The verification model showed the combination of MTRasym (3.5 ppm), D, and SUVmax had the strongest predictive value, and its ROC curve and calibration curve showed good accuracy (AUC, 0.919, 95% CI: 0.891-0.937) and consistency. Conclusions: Multi-parametric 18F-FDG PET/MRI is beneficial for the non-invasive assessment of PD-L1 status in NSCLC patients, and the combination of SUVmax, D, and MTRasym (3.5 ppm) may serve as a prognostic biomarker to guide immunotherapy.

IVIM Imaging of Paraspinal Muscles Following Moderate and High-Intensity Exercise in Healthy Individuals.

Background: Quantification of the magnitude and spatial distribution of muscle blood flow changes following exercise may improve our understanding of the effectiveness of various exercise prescriptions. Intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) is a technique that quantifies molecular diffusion and microvascular blood flow, and has recently gained momentum as a method to evaluate a muscle's response to exercise. It has also been shown to predict responses to exercise-based physical therapy in individuals with low back pain. However, no study has evaluated the sensitivity of IVIM-MRI to exercise of varying intensity in humans. Here, we aimed to evaluate IVIM signal changes of the paraspinal muscles in response to moderate and high intensity lumbar extension exercise in healthy individuals. Methods: IVIM data were collected in 11 healthy volunteers before and immediately after a 3-min bout of moderate and high-intensity resisted lumbar extension. IVIM data were analyzed to determine the average perfusion fraction (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D) in the bilateral paraspinal muscles. Changes in IVIM parameters were compared between the moderate and high intensity exercise bouts. Results: Exercise increased all IVIM parameters, regardless of intensity (p < 0.003). Moderate intensity exercise resulted in a 11.2, 19.6, and 3.5% increase in f, D* and D, respectively. High intensity exercise led to a similar increase in f (12.2%), but much greater changes in D* (48.6%) and D (7.9%). Conclusion: IVIM parameter increases suggest that both the moderate and high-intensity exercise conditions elicited measurable changes in blood flow (increased f and D*) and extravascular molecular diffusion rates (increased D), and that there was a dose-dependence of exercise intensity on D* and D.

Bi-exponential fitting excluding b=0 data improves the scan-rescan stability of liver IVIM parameter measures and particularly so for the perfusion fraction.

Background: A prerequisite to translating intravoxel incoherent motion (IVIM) imaging into meaningful clinical applications is sufficient scan-rescan reproducibility. This study aims to confirm the hypothesis that IVIM data fitting by not using b=0 images will improve the stability of liver IVIM measurement. Methods: Healthy volunteers' liver IVIM images were prospectively acquired using a 1.5-T magnet or a 3.0 T with 16 b-values. Repeatability study subjects were scanned twice during the same session, resulted in 35 paired scans for 35 subjects (11 men, mean age: 41.82 years, range: 32-60 years; 24 women, mean age: 42.67 years, range: 20-71 years). IVIM analysis was performed with full-fitting and segmented-fitting with a threshold b-value of 60 s/mm2, and fitting started from b=0 s/mm2 or from b=2 s/mm2. Reproducibility study subjects were scanned and then rescanned with an interval of 5-18 days, resulted in 20 paired scans for 11 subjects (4 men, mean age: 26.25 years, range: 25-27 years; 7 women, mean age: 25.57 years, range: 24-27 years). IVIM analysis was performed with segmented-fitting with a threshold b-value of 50 s/mm2, and fitting started from b=0 s/mm2 or from b=3 s/mm2. Results: Fitting without b=0 data generally improved the repeatability and reproducibility for both PF and Dslow, and particularly so for PF. For with b=0 data segmented fitting repeatability, PF had within-subject standard deviation of 0.019, bland-Atman 75% agreement limit of -31.52% to 28.35%, and ICC of 0.647, while these values were 0.009, -20.78% to 16.86%, and 0.837 for without b=0 analysis. Though the repeatability and reproducibility for Dfast generally also improved, they remained suboptimal. Measurement stability was better for repeatability than for reproducibility. Conclusions: Scan-rescan repeatability and reproducibility of liver IVIM parameters can be improved by fitting without b=0 data, which is particularly so for PF.

Usefulness of diffusion derived vessel density computed from a simplified IVIM imaging protocol: An experimental study with rat biliary duct blockage induced liver fibrosis.

OBJECTIVES: Liver vessel density can be evaluated by DDVD (diffusion derived vessel density): DDVD(b0b1) = Sb0/ROIarea0 - Sb1/ROIarea1, where Sb0 and Sb1 refer to the liver signal when b is 0 or 1 s/mm2. Sb1 and ROIarea1 may be replaced by other b-values. With a rat biliary duct ligation (BDL) model, this study assesses the usefulness of liver DDVD computed from a simplified IVIM imaging protocol using b = 25 and b = 50 to replace b = 1 s/mm2, alone and in combination with other IVIM parameters. METHODS: Male Sprague-Dawley rats were used. The rat number was 5, 5, 5, and 3 respectively, for the timepoints of 7, 14, 21, 28 days post-BDL surgery. 12 rats had partial biliary duct recanalization performed after the rats had BDL for 7 days and then again followed-up for a mean of 14 days. Liver diffusion MRIs were acquired at 3.0 T with a b-value distribution of 0, 25, 50, 75, 100, 150, 300, 700, 1000 s/mm2. DDVDmean (control rats n = 6) was the mean of DDVD(b0b25) and DDVD(b0b50). IVIM fitting started from b = 0 s/mm2 with segmented fitting and a threshold b of 50 s/mm2 (n = 5 for control rats). Three 3-D spaces were constructed using a combination of the four diffusion parameters. RESULTS: The control rats and BDL rats (n = 18) had a liver DDVDmean of 84.0 ± 26.2 and 44.7 ± 14.4 au/pixel (p < 0.001). All 3-D spaces totally separated healthy livers and all fibrotic livers (n = 30, BDL rats and recanalization rats). The mean relative distance between healthy liver cluster and fibrotic liver cluster was 0.331 for PF, Dslow, and Dfast; 0.381 for PF, Dfast, and DDVDmean; and 0.384 for PF, Dslow, and DDVDmean. CONCLUSION: A combination of PF, Dslow, and Dfast allows total separation of healthy livers and fibrotic livers and the integration of DDVD improved the separation.