Diffusion-weighted MRI in early chemotherapy response evaluation of patients with diffuse large B-cell lymphoma--a pilot study: comparison with 2-deoxy-2-fluoro- D-glucose-positron emission tomography/computed tomography

To determine the feasibility of diffusion‐weighted MRI (DWI) in the evaluation of the early chemotherapeutic response in patients with aggressive non‐Hodgkin's lymphoma (NHL), eight patients with histologically proven diffuse large B‐cell lymphoma were imaged by MRI, including DWI, and positron emission tomography/computed tomography (PET/CT) before treatment (E1), and after 1 week (E2) and two cycles (E3) of chemotherapy. In all patients, whole‐body screening using T₁‐ and T₂‐weighted images in the coronal plane was performed. To quantitatively evaluate the chemotherapeutic response, axial images including DWI were acquired. Apparent diffusion coefficient (ADC) maps were reconstructed, and the ADC value of the tumor was measured. In addition, the tumor volume was estimated on axial T₂‐weighted images. The maximum standardized uptake value (SUV_max) and active tumor volume were measured on fused PET/CT images. Lymphomas showed high signal intensity on DW images and low signal intensity on ADC maps, except for necrotic foci. The mean pre‐therapy ADC was 0.71 × 10^?3 mm²/s; it increased by 77% at E2 (p < 0.05) and 24% more at E3 (insignificant); the total increase was 106% (p < 0.05). The mean tumor volume by MRI was 276 mL at baseline; it decreased by 58% at E2 (p < 0.05) and 65% more at E3 (p < 0.05), giving a total decrease of 84% (p < 0.05). All the imaged pre‐therapy tumors were strongly positive on PET/CT, with a mean SUV_max of 20. The SUV_max decreased by 60% at E2 (p < 0.05) and 59% more at E3 (p < 0.05), giving a total decrease of 83% (p < 0.05). The active tumor burden decreased by 66% at E2 (p < 0.05). At baseline, both central and peripheral tumor ADC values correlated inversely with SUV_max (p < 0.05), and also correlated inversely with active tumor burden on PET/CT and with tumor volume on MRI at E2 (p < 0.05). In conclusion, the results of DWI in combination with whole‐body MRI were comparable with those of integrated PET/CT. Copyright © 2011 John Wiley & Sons, Ltd.     

Diffusion‐weighted MRI for staging and evaluation of response in diffuse large B‐cell lymphoma: a pilot study

The aim of this study was to compare diffusion‐weighted MRI (DW‐MRI) with positron emission tomography/computed tomography (PET/CT) for the staging and evaluation of the treatment response in patients with diffuse large B‐cell lymphoma (DLBCL). Institutional review board approval was obtained for this study; all subjects gave informed consent. Twelve patients were imaged before treatment and eight of these were also imaged after two cycles of chemotherapy using both DW‐MRI and PET/CT. Up to six target lesions were selected at baseline for response assessment based on International Working Group criteria (nodes > 1.5 cm in diameter; extranodal lesions > 1 cm in diameter). For pretreatment staging, visual analysis of the numbers of nodal and extranodal lesions based on PET/CT was performed. For interim response assessment after cycle 2 of chemotherapy, residual tumor sites were assessed visually and the percentage changes in target lesion size, maximum standardized uptake value (SUV_max) and apparent diffusion coefficient (ADC) from pretreatment values were calculated. In 12 patients studied pretreatment, there were 46 nodal and 16 extranodal sites of lymphomatous involvement. Agreement between DW‐MRI and PET/CT for overall lesion detection was 97% (60/62 tumor sites; 44/46 nodal and 16/16 extranodal lesions) and, for Ann Arbor stage, it was 100%. In the eight patients who had interim assessment, five of their 49 tumor sites remained abnormal on visual analysis of both DW‐MRI and PET/CT, and there was one false positive on DW‐MRI. Of their 24 target lesions, the mean pretreatment ADC value, tumor size and SUV_max were 772 µm²/s, 21.3 cm² and 16.9 g/mL, respectively. At interim assessment of the same 24 target lesions, ADC values increased by 85%, tumor size decreased by 74% and SUV_max decreased by 83% (all p < 0.01 versus baseline). DW‐MRI provides results comparable with those of PET/CT for staging and early response assessment in patients with DLBCL. Copyright © 2014 John Wiley & Sons, Ltd.     

Fast diffusion kurtosis imaging (DKI) with Inherent COrrelation‐based Normalization (ICON) enhances automatic segmentation of heterogeneous diffusion MRI lesion in acute stroke

Diffusion kurtosis imaging (DKI) has been shown to augment diffusion‐weighted imaging (DWI) for the definition of irreversible ischemic injury. However, the complexity of cerebral structure/composition makes the kurtosis map heterogeneous, limiting the specificity of kurtosis hyperintensity to acute ischemia. We propose an Inherent COrrelation‐based Normalization (ICON) analysis to suppress the intrinsic kurtosis heterogeneity for improved characterization of heterogeneous ischemic tissue injury. Fast DKI and relaxation measurements were performed on normal (n = 10) and stroke rats following middle cerebral artery occlusion (MCAO) (n = 20). We evaluated the correlations between mean kurtosis (MK), mean diffusivity (MD) and fractional anisotropy (FA) derived from the fast DKI sequence and relaxation rates R₁ and R₂, and found a highly significant correlation between MK and R₁ (p < 0.001). We showed that ICON analysis suppressed the intrinsic kurtosis heterogeneity in normal cerebral tissue, enabling automated tissue segmentation in an animal stroke model. We found significantly different kurtosis and diffusivity lesion volumes: 147 ± 59 and 180 ± 66 mm³, respectively (p = 0.003, paired t‐test). The ratio of kurtosis to diffusivity lesion volume was 84% ± 19% (p < 0.001, one‐sample t‐test). We found that relaxation‐normalized MK (RNMK), but not MD, values were significantly different between kurtosis and diffusivity lesions (p < 0.001, analysis of variance). Our study showed that fast DKI with ICON analysis provides a promising means of demarcation of heterogeneous DWI stroke lesions.     

The Value of 18F-FDG PET/CT in Evaluating Disease Severity and Prognosis in Idiopathic Pulmonary Fibrosis Patients

BackgroundSeveral parameters are useful for assessing disease severity in idiopathic pulmonary fibrosis (IPF); however, the role of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is not well-defined. We aimed to evaluate the value of ¹⁸F-FDG PET/CT for assessing disease severity and prognosis in IPF patients.MethodsClinical data of 89 IPF patients (mean age: 68.1 years, male: 94%) who underwent ¹⁸F-FDG PET/CT for evaluation of lung nodules or cancer staging were retrospectively reviewed. Mean and maximal standardized uptake values (SUV_mean, SUV_max, respectively) were measured in the fibrotic area. Adjusted SUV, including SUV ratio (SUVR, defined as SUV_max-to-liver SUV_mean ratio), tissue fraction-corrected SUV_mean (SUV_meanTF), and SUVR (SUVR_TF), and tissue-to-blood ratio (SUV_max/SUV_mean venous; TBR_blood) were obtained. Death was defined as the primary outcome, and associations between other clinical parameters (lung function, exercise capacity, C-reactive protein [CRP] level) were also investigated.ResultsAll SUV parameters were inversely correlated with the forced vital capacity, diffusing capacity for carbon monoxide, and positively correlated with CRP level and the gender-age-physiology index. The SUV_mean, SUV_max, and SUV_meanTF were associated with changes in lung function at six months. The SUVR (hazard ratio [HR], 1.738; 95% confidence interval [CI], 1.011–2.991), SUVR_TF (HR, 1.441; 95% CI, 1.000–2.098), and TBR_blood (HR, 1.377; 95% CI, 1.038–1.827) were significant predictors for mortality in patients with IPF in the univariate analysis, but not in the multivariate analysis.Conclusion¹⁸F-FDG PET/CT may provide additional information on the disease severity and prognosis in IPF patients, and the SUVR may be superior to other SUV parameters.     

A multi‐Gaussian model for apparent diffusion coefficient histogram analysis of Wilms’ tumour subtype and response to chemotherapy

Wilms’ tumours (WTs) are large heterogeneous tumours, which typically consist of a mixture of histological cell types, together with regions of chemotherapy‐induced regressive change and necrosis. The predominant cell type in a WT is assessed histologically following nephrectomy, and used to assess the tumour subtype and potential risk. The purpose of this study was to develop a mathematical model to identify subregions within WTs with distinct cellular environments in vivo, determined using apparent diffusion coefficient (ADC) values from diffusion‐weighted imaging (DWI). We recorded the WT subtype from the histopathology of 32 tumours resected in patients who received DWI prior to surgery after pre‐operative chemotherapy had been administered. In 23 of these tumours, DWI data were also available prior to chemotherapy. Histograms of ADC values were analysed using a multi‐Gaussian model fitting procedure, which identified ‘subpopulations’ with distinct cellular environments within the tumour volume. The mean and lower quartile ADC values of the predominant viable tissue subpopulation (ADC_1MEAN, ADC_1LQ), together with the same parameters from the entire tumour volume (ADC_0MEAN, ADC_0LQ), were tested as predictors of WT subtype. ADC_1LQ from the multi‐Gaussian model was the most effective parameter for the stratification of WT subtype, with significantly lower values observed in high‐risk blastemal‐type WTs compared with intermediate‐risk stromal, regressive and mixed‐type WTs (p < 0.05). No significant difference in ADC_1LQ was found between blastemal‐type and intermediate‐risk epithelial‐type WTs. The predominant viable tissue subpopulation in every stromal‐type WT underwent a positive shift in ADC_1MEAN after chemotherapy. Our results suggest that our multi‐Gaussian model is a useful tool for differentiating distinct cellular regions within WTs, which helps to identify the predominant histological cell type in the tumour in vivo. This shows potential for improving the risk‐based stratification of patients at an early stage, and for guiding biopsies to target the most malignant part of the tumour. Copyright © 2015 John Wiley & Sons, Ltd.     

Intraventricular temperature measured by diffusion‐weighted imaging compared with brain parenchymal temperature measured by MRS in vivo

We examined and compared the temperatures of the intraventricular cerebrospinal fluid (T_v) and the brain parenchyma (T_p) using MRI, with reference to the tympanic membrane temperature (T_t) in healthy subjects. We estimated T_v and T_p values from data gathered simultaneously by MR diffusion‐weighted imaging (DWI) and MRS, respectively, in 35 healthy volunteers (17 males, 18 females; age 25–78 years). We also obtained T_t values just before each MR examination to evaluate the relationships among the three temperatures. There were significant positive correlations between T_v and T_p (R = 0.611, p < 0.001). The correlation was also significant after correction for T_t (R = 0.642, p < 0.001). There was no significant correlation between T_v and T_t or between T_p and T_t in the men or the women. Negative correlations were found between T_v and age and between T_p and age in the males but not females. DWI thermometry seems to reflect the intracranial environment as accurately as MRS thermometry. An age‐dependent decline in temperature was evident in our male subjects by both DWI and MRS thermometry, probably due to the decrease in cerebral metabolism with age. Copyright © 2016 John Wiley & Sons, Ltd.     

Pilot Study: Evaluation of Dual-Energy Computed Tomography Measurement Strategies for Positron Emission Tomography Correlation in Pancreatic Adenocarcinoma

We sought to determine whether dual-energy computed tomography (DECT) measurements correlate with positron emission tomography (PET) standardized uptake values (SUVs) in pancreatic adenocarcinoma, and to determine the optimal DECT imaging variables and modeling strategy to produce the highest correlation with maximum SUV (SUV_max). We reviewed 25 patients with unresectable pancreatic adenocarcinoma seen at Mayo Clinic, Scottsdale, Arizona, who had PET–computed tomography (PET/CT) and enhanced DECT performed the same week between March 25, 2010 and December 9, 2011. For each examination, DECT measurements were taken using one of three methods: (1) average values of three tumor regions of interest (ROIs) (method 1); (2) one ROI in the area of highest subjective DECT enhancement (method 2); and (3) one ROI in the area corresponding to PET SUV_max (method 3). There were 133 DECT variables using method 1, and 89 using the other methods. Univariate and multivariate analysis regression models were used to identify important correlations between DECT variables and PET SUV_max. Both R² and adjusted R² were calculated for the multivariate model to compensate for the increased number of predictors. The average SUV_max was 5 (range, 1.8–12.0). Multivariate analysis of DECT imaging variables outperformed univariate analysis (r = 0.91; R² = 0.82; adjusted R² = 0.75 vs r < 0.58; adjusted R² < 0.34). Method 3 had the highest correlation with PET SUV_max (R² = 0.82), followed by method 1 (R² = 0.79) and method 2 (R² = 0.57). DECT thus has clinical potential as a surrogate for, or as a complement to, PET in patients with pancreatic adenocarcinoma.     

Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B‐cell lymphoma – a whole‐body MRI and diffusion‐weighted imaging study

To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B‐cell lymphoma (DLBCL), 18 patients with histology‐confirmed DLBCL underwent 3‐T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T₁‐weighted pre‐ and post‐contrast, T₂‐weighted with and without fat suppression, and a single‐shot echo‐planar diffusion‐weighted imaging (DWI) with two b values (0 and 800 s/mm²). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T₂‐weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T₂‐weighted image with fat suppression decreased significantly (p < 0.01), and that of the T₁‐weighted pre‐contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 × 10^–3 mm²/s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = ?0.62, p < 0.01). In conclusion, this study indicates that T₂‐weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI. Copyright © 2013 John Wiley & Sons, Ltd.     

Acute renal impairment characterization using diffusion magnetic resonance imaging: Validation by histology

Diffusion magnetic resonance imaging has been demonstrated to be a simple, noninvasive and accurate method for the detection of renal microstructure and microcirculation, which are closely linked to renal function. Moreover, serum endothelin‐1 (ET‐1) was also reported as a good indicator of early renal injury. The aim of this study was to evaluate the feasibility and capability of diffusion MRI and ET‐1 to detect acute kidney injury by an operation simulating high‐pressure renal pelvic perfusion, which is commonly used during ureteroscopic lithotripsy. Histological findings were used as a reference. Fourteen New Zealand rabbits in an experimental group and 14 in a control group were used in this study. Diffusion tensor imaging and intravoxel incoherent motion diffusion‐weighted imaging were acquired by a 3.0 T MRI scanner. Significant corticomedullary differences were found in the values of the apparent diffusion coefficient (ADC), pure tissue diffusion, volume fraction of pseudo‐diffusion (fp) and fractional anisotropy (FA) (P < 0.05 for all) in both preoperation and postoperation experimental groups. Compared with the control group, the values of cortical fp_mean, medullary ADC_mean and FA_mean decreased significantly (P < 0.05) after the operation in the experimental group. Also, the change rate of medullary ADC_mean in the experimental group was more pronounced than that in the control group (P = 0.018). No significant change was found in serum ET‐1 concentration after surgery in either the experimental (P = 0.80) or control (P = 0.17) groups. In the experimental group, histological changes were observed in the medulla, while no visible change was found in the cortex. This study demonstrated the feasibility of diffusion MRI to detect the changes of renal microstructure and microcirculation in acute kidney injury, with the potential to evaluate renal function. Moreover, the sensitivity of diffusion MRI to acute kidney injury appears to be superior to that of serum ET‐1.     

Predictive significance of standardized uptake value parameters of FDG-PET in patients with non-small cell lung carcinoma

¹⁸F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is widely used to diagnose and stage non-small cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the predictive ability of different FDG standardized uptake values (SUVs) in 74 patients with newly diagnosed NSCLC. ¹⁸F-FDG PET/CT scans were performed and different SUV parameters (SUV_max, SUV_avg, SUV_T/L, and SUV_T/A) obtained, and their relationship with clinical characteristics were investigated. Meanwhile, correlation and multiple stepwise regression analyses were performed to determine the primary predictor of SUVs for NSCLC. Age, gender, and tumor size significantly affected SUV parameters. The mean SUVs of squamous cell carcinoma were higher than those of adenocarcinoma. Poorly differentiated tumors exhibited higher SUVs than well-differentiated ones. Further analyses based on the pathologic type revealed that the SUV_max, SUV_avg, and SUV_T/L of poorly differentiated adenocarcinoma tumors were higher than those of moderately or well-differentiated tumors. Among these four SUV parameters, SUV_T/L was the primary predictor for tumor differentiation. However, in adenocarcinoma, SUV_max was the determining factor for tumor differentiation. Our results showed that these four SUV parameters had predictive significance related to NSCLC tumor differentiation; SUV_T/L appeared to be most useful overall, but SUV_max was the best index for adenocarcinoma tumor differentiation.     

Relationship between Preoperative 18F-Fluorodeoxyglucose Uptake and Epidermal Growth Factor Receptor Status in Primary Colorectal Cancer

Purpose

Both ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) uptake and epidermal growth factor receptor (EGFR) status are prognostic variables of colorectal cancer (CRC). The aim of this study was to investigate a possible association between ¹⁸F-FDG uptake on preoperative positron emission tomography/computed tomography (PET/CT) and EGFR status in primary CRC.

Materials and Methods

Records of 132 patients (66 men and 66 women; mean age=67.1±11.1 years) who underwent ¹⁸F-FDG PET/CT for CRC staging and subsequent bowel resection were reviewed. In primary lesions, ¹⁸F-FDG uptake was semiquantitatively evaluated in terms of maximum standardized uptake value (SUV_max), and EGFR status was determined by immunohistochemistry. Associations of clinicopathological parameters and EGFR status were analyzed by Pearson''s chi-square test, multiple logistic regression, and receiver operating characteristic curves.

Results

Eighty-six patients (65.2%) showed EGFR expression. SUV_max was significantly lower in EGFR-negative tumors than in EGFR-expressing tumors (10.0±4.2 vs. 12.1±2.1; p=0.012). It was the only significant parameter correlated with EGFR expression (odds ratio=2.457; relative risk=2.013; p=0.038). At the SUV_max threshold of 7.5, the sensitivity and specificity for predicting EGFR expression were 84.9% and 40.4%, respectively (area under the curve=0.624; p=0.019).

Conclusion

Preoperative ¹⁸F-FDG uptake is slightly correlated with EGFR status in primary CRC. Preoperative SUV_max of ¹⁸F-FDG may have a limited role in predicting EGFR expression in such tumors because of its poor specificity.     

Validation of fast diffusion kurtosis MRI for imaging acute ischemia in a rodent model of stroke

Diffusion‐weighted imaging (DWI) captures ischemic tissue that is likely to infarct, and has become one of the most widely used acute stroke imaging techniques. Diffusion kurtosis imaging (DKI) has lately been postulated as a complementary MRI method to stratify the heterogeneously damaged DWI lesion. However, the conventional DKI acquisition time is relatively long, limiting its use in the acute stroke setting. Recently, a fast kurtosis mapping method has been demonstrated in fixed brains and control subjects. The fast DKI approach provides mean diffusion and kurtosis measurements under substantially reduced scan time, making it amenable to acute stroke imaging. Because it is not practical to obtain and compare different means of DKI to test whether the fast DKI method can reliably detect diffusion and kurtosis lesions in acute stroke patients, our study investigated its diagnostic value using an animal model of acute stroke, a critical step before fast DKI acquisition can be routinely applied in the acute stroke setting. We found significant correlation, per voxel, between the diffusion and kurtosis coefficients measured using the fast and conventional DKI protocols. In acute stroke rats, the two DKI methods yielded diffusion and kurtosis lesions that were in good agreement. Importantly, substantial kurtosis–diffusion lesion mismatch was observed using the conventional (26 ± 13%, P < 0.01) and fast DKI methods (23 ± 8%, P < 0.01). In addition, regression analysis showed that the kurtosis–diffusion lesion mismatches obtained using conventional and fast DKI methods were substantially correlated (R² = 0.57, P = 0.02). Our results confirmed that the recently proposed fast DKI method is capable of capturing heterogeneous diffusion and kurtosis lesions in acute ischemic stroke, and thus is suitable for translational applications in the acute stroke clinical setting. Copyright © 2014 John Wiley & Sons, Ltd.     

Prediction of pathologic response to neoadjuvant chemotherapy in patients with breast cancer using diffusion‐weighted imaging and MRS

The aim of this study was to determine whether tumor size, MRS parameters and apparent diffusion coefficient (ADC) measurements could be applied to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Ninety patients with breast cancer (median size, 4.5 cm; range, 1.6–9.5 cm) were evaluated with single‐voxel ¹H MRS and dynamic contrast‐enhanced MRI. Diffusion‐weighted imaging was performed in 41 of these patients using a 1.5‐T scanner before and after completion of NAC. Pre‐ and post‐treatment measurements and changes in tumor size, MRS parameters [absolute and normalized total choline‐containing compound (tCho) integral and tCho signal‐to‐noise ratio (SNR)] and ADCs in pCR versus non‐pCR were compared using the nonparametric Mann–Whitney test. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of each parameter. After NAC, 30 patients (33%) showed pCR and 60 (67%) showed non‐pCR. At pretreatment, ADC was the only significant parameter in differentiating between pCR and non‐pCR [(0.83 ± 0.05) × 10^–3 versus (0.97 ± 0.14) × 10^–3 mm²/s] (p = 0.014). Post‐treatment measurements after completion of NAC and changes in tumor size (both p < 0.001), MRS parameters (p = 0.027 and p = 0.020 for absolute tCho integral, p = 0.036 and p = 0.023 for normalized tCho integral, and p = 0.032 and p = 0.061 for tCho SNR) and ADC (p = 0.003 and p < 0.001) were significantly different between the pCR and non‐pCR groups, except for changes in tCho SNR. In ROC analysis, the areas under the ROC curve (AUCs) of 0.63–0.73 were obtained for tumor size and MRS parameters. AUCs for pre‐ and post‐treatment ADC and changes in ADC were 0.75, 0.80 and 0.96, respectively. The optimal cut‐off of the percentage change in ADC for predicting pCR was 40.7%, yielding 100% sensitivity and 91% specificity. Patients with pCR showed significantly lower pretreatment ADCs than those with non‐pCR. The change in ADC after NAC was the most accurate predictor of pCR. Copyright © 2012 John Wiley & Sons, Ltd.     

Interstitial fluid pressure correlates with intravoxel incoherent motion imaging metrics in a mouse mammary carcinoma model

The effective delivery of a therapeutic drug to the core of a tumor is often impeded by physiological barriers, such as the interstitial fluid pressure (IFP). There are a number of therapies that can decrease IFP and induce tumor vascular normalization. However, a lack of a noninvasive means to measure IFP hinders the utilization of such a window of opportunity for the maximization of the treatment response. Thus, the purpose of this study was to investigate the feasibility of using intravoxel incoherent motion (IVIM) diffusion parameters as noninvasive imaging biomarkers for IFP. Mice bearing the 4T1 mammary carcinoma model were studied using diffusion‐weighted imaging (DWI), immediately followed by wick‐in‐needle IFP measurement. Voxelwise analysis was conducted with a conventional monoexponential diffusion model, as well as a biexponential model taking IVIM into account. There was no significant correlation of IFP with either the median apparent diffusion coefficient from the monoexponential model (r = 0.11, p = 0.78) or the median tissue diffusivity from the biexponential model (r = 0.30, p = 0.44). However, IFP was correlated with the median pseudo‐diffusivity (D_p) of apparent vascular voxels (r = 0.76, p = 0.02) and with the median product of the perfusion fraction and pseudo‐diffusivity (f_pD_p) of apparent vascular voxels (r = 0.77, p = 0.02). Although the effect of IVIM in tumors has been reported previously, to our knowledge, this study represents the first direct comparison of IVIM metrics with IFP, with the results supporting the feasibility of the use of IVIM DWI metrics as noninvasive biomarkers for tumor IFP. Copyright © 2011 John Wiley & Sons, Ltd.     

Time‐dependent diffusion MRI as a probe of microstructural changes in a mouse model of Duchenne muscular dystrophy

Dystrophic muscles show a high variability of fibre sizes and altered sarcolemmal integrity, which are typically assessed by histology. Time‐dependent diffusion MRI is sensitive to tissue microstructure and its investigation through age‐related changes in dystrophic and healthy muscles may help the understanding of the onset and progression of Duchenne muscular dystrophy (DMD). We investigated the capability of time‐dependent diffusion MRI to quantify age and disease‐related changes in hind‐limb muscle microstructure between dystrophic (mdx) and wild‐type (WT) mice of three age groups (7.5, 22 and 44 weeks). Diffusion time‐dependent apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined versus age and diffusion‐gradient orientation at six diffusion times (Δ; range: 25–350 ms). Mean muscle ADCs were compared between groups and ages, and correlated with T₂, using Student's t test, one‐way analysis of variance and Pearson correlation, respectively. Muscle fibre sizes and sarcolemmal integrity were evaluated by histology and compared with diffusion measurements. Hind‐limb muscle ADC showed characteristic restricted diffusion behaviour in both mdx and WT animals with decreasing ADC values at longer Δ. Significant differences in ADC were observed at long Δ values (≥ 250 ms; p < 0.05, comparison between groups; p < 0.01, comparison between ages) with ADC increased by 5–15% in dystrophic muscles, indicative of reduced diffusion restriction. No significant correlation was found between T₂ and ADC. Additionally, muscle fibre size distributions showed higher variability and lower mean fibre size in mdx than WT animals (p < 0.001). The extensive Evans Blue Dye uptake shown in dystrophic muscles revealed substantial sarcolemmal damage, suggesting diffusion measurements as more consistent with altered permeability rather than changes in muscle fibre sizes. This study shows the potential of diffusion MRI to non‐invasively discriminate between dystrophic and healthy muscles with enhanced sensitivity when using long Δ.     

Surveillance Imaging after Autologous Hematopoietic Cell Transplantation Predicts Survival in Patients with Diffuse Large B Cell Lymphoma

The utility of surveillance imaging after autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory diffuse large B cell lymphoma (DLBCL) remains unclear. The purpose of this study was to determine whether surveillance imaging predicts survival after AHCT. At the University of Minnesota, serial imaging for early relapse detection has been used prospectively for all consecutive AHCT recipients treated since 2010. The present analysis included 91 AHCT recipients with DLBCL who underwent ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) scan at day +100 post-AHCT. ¹⁸F-FDG-PET parameters included the Deauville (D) 5-point scale, peak standardized uptake values (SUV_max), total legion glycolysis (TLG), and total metabolic tumor volume (TMTV). Survival of patients with clinically symptomatic versus asymptomatic radiographically detected relapsed DLBCL after AHCT was compared. Sixty patients experienced relapse; 35% was detected on day +100 surveillance PET scan. 5-year overall survival (OS) by ¹⁸F-FDG-PET scan at day +100 post-AHCT was significantly lower in D4 and D5 patients (37%; 95% confidence interval [CI], 14% to 100% versus 25%; 95% CI, 43% to 89%) compared with patients with D1 and D2 (62%; 95% CI, 43% to 89% versus 62%; 95% CI, 46% to 84%). TLG and TMTV were not prognostic. SUV_max at day +100 varied from 1.5 (D1) to 17.9 (D5). In multivariate analysis, only SUV_max was predictive of relapse and OS; mortality increased 1.8-fold with each SUV_max doubling (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.3; P < .01). At a median follow-up of 3.3 years (range, 1 to 12 years), lymphoma-related mortality was 1.8-fold higher among patients whose relapse was detected clinically (symptomatic) versus radiographically on surveillance scan (HR, 1.8; 95% CI, .9 to 3.4; P = .08). In patients with relapsed/refractory DLBCL, a routine PET imaging at day +100 post-AHCT detects asymptomatic relapse and high SUV_max identifies patients with poor expected survival of less than 1 year. Identifying this high-risk cohort can potentially highlight patients who might benefit from preemptive interventions to prevent or delay relapse.     

Positron Emission Tomography–Based Assessment of Metabolic Tumor Volume Predicts Survival after Autologous Hematopoietic Cell Transplantation for Hodgkin Lymphoma

Autologous hematopoietic cell transplantation (AHCT) is curative for 60% of patients with relapsed or refractory Hodgkin lymphoma (R/R HL). A more precise assessment of the depth of remission before AHCT may help to identify patients likely to benefit from AHCT. We aimed to determine whether positron emission tomography (PET)-based quantitative parameters of total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and maximal standardized uptake volume (SUV_max) measured before AHCT predict progression-free survival (PFS) after transplant. Pretransplant PET/computed tomography images of 96 consecutive patients with R/R HL were analyzed. Median TMTV, TLG, and SUV_max were 7.97?cm³ (range, 1.3 to 102.1), 23.7 (range, 4.0 to 813.1), and 5.23 (range, 2.7 to 23.2). Two-year PFS in patients with high TMTV (TMTVhigh; more than median; n?=?17) was only 12% (95% CI, 1% to 38%) compared with 53% (95% CI, 28% to 73%; P?=?.05) in patients with TMTVlow (lower or equal to median; n?=?17) and 63% (95% CI, 50% to 74%) in 61 patients with no metabolically active tumor (TMTV0; P?>?.01). In concordance, high TLG (>19) and SUV_max (>4.9) predicted inferior 2-year PFS. In multivariate analysis patients with TMTVhigh had a 3.5-fold higher risk of treatment failure compared with TMTV0/TMTVlow (HR, 3.49; 95% CI, 1.75 to 6.93; P?<?.01). Deauville (D)-scores of 4 to 5 before AHCT predicted worse PFS compared with D-scores of 1 to 3 (HR, 3.7; 95% CI, 1.92 to 7.28; P?<?.01). Yet, TMTV and D-scores were disconcordant in 12 subjects; 9 patients in the D4 group with TMTVlow had 2-year PFS of 44% (95% CI, 14% to 72%), which was 2-fold higher than predicted by D4 score. In conclusion, in patients with R/R HL and PET-positive residual disease, TMTVhigh can identify very poor AHCT responders. Patients with TMTVlow, TLG, and SUV_max before AHCT have similar outcomes to those without metabolically active disease.     

Correlation between heart rate and performance during Olympic windsurfing competition

The aim of this study was to examine the heart rate (HR) response to Olympic windsurfing competition and to check if there was any correlation between racing HR, performance, and the variables measured during laboratory maximal exercise. Ten elite windsurfers [age: 20.93 (3.46) years; height: 178.10 (6.34) cm; body mass: 66.79 (5.90) kg] performed a laboratory maximal oxygen consumption (VO_2max) trial and national windsurf competitions wearing a HR monitor. One hundred and forty-three individual races were examined. Racing HR was expressed as a percentage of (1) HR_max (maximal treadmill HR) and (2) HR_reserve (HR_max−HR_rest). The performance (racing classification: RC, which is inversely proportional to performance) was significantly correlated to the racing HR response in both light wind (LW): LW−RC=−0.12(%HR_reserve)+13.03; r=−0.71, r ²=0.50, p<0.001, and medium wind (MW): MW−RC=−0.11(%HR_reserve)+10.99; r=−0.66, r ²=0.43, p<0.001. The results showed similar correlations between performance and %HR_max. Post racing lactate concentration was higher in LW compared to MW [7.14 (0.21) and 5.18 (2.02) mmol·l⁻¹, respectively]. There was a negative correlation between the highest racing HR (%HR_reserve) of each athlete and the second ventilatory threshold expressed as a percentage of VO˙_2max (r=–0.71, p<0.05). To summarize, this study showed that light and medium wind Olympic windsurfing performances are highly dependent on the capacity of the athlete to maintain a high HR for long periods of time. Furthermore, windsurfing is highly dependent on the athlete's physical fitness level as shown by the correlations between racing HRs and laboratory physiological variables. Electronic Publication     

Middle cerebral artery blood velocity during exercise with β‐1 adrenergic and unilateral stellate ganglion blockade in humans

A reduced ability to increase cardiac output (CO) during exercise limits blood flow by vasoconstriction even in active skeletal muscle. Such a flow limitation may also take place in the brain as an increase in the transcranial Doppler determined middle cerebral artery blood velocity (MCA V_mean) is attenuated during cycling with β‐1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocain; 8 mL; n=8) affects the attenuated exercise – MCA V_mean following cardio‐selective β‐1 adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.) during cycling. Cardiac output determined by indocyanine green dye dilution, heart rate (HR), mean arterial pressure (MAP) and MCA V_mean were obtained during moderate intensity cycling before and after pharmacological intervention. During control cycling the right and left MCA V_mean increased to the same extent (11.4 ± 1.9 vs. 11.1 ± 1.9 cm s^?1). With the pharmacological intervention the exercise CO (10 ± 1 vs. 12 ± 1 L min^?1; n=5), HR (115 ± 4 vs. 134 ± 4 beats min^?1) and ΔMCA V_mean (8.7 ± 2.2 vs. 11.4 ± 1.9 cm s^?1) were reduced, and MAP was increased (100 ± 5 vs. 86 ± 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck eliminated the β‐1 blockade induced attenuation in ΔMCA V_mean (10.2 ± 2.5 cm s^?1). These results indicate that a reduced ability to increase CO during exercise limits blood flow to a vital organ like the brain and that this flow limitation is likely to be by way of the sympathetic nervous system.