Apparent Diffusion Coefficient Changes Research Articles

Multimodal functional imaging for early response assessment in patients with gastrointestinal stromal tumor treated with tyrosine kinase inhibitors.

Several imaging modalities are used in the early work-up of patients with gastrointestinal stromal tumor (GIST) receiving tyrosine kinase inhibitor (TKI) treatment and there is a need to establish whether they provide similar or complimentary information. To compare 18F-fluorodeoxyglucose positron emission tomography (FDG PET), computed tomography (CT) and magnetic resonance imaging (MRI) as early predictors of three-month outcomes for patients with GIST receiving TKI treatment. Thirty-five patients with advanced GIST were prospectively included between February 2011 and June 2017. FDG PET, contrast-enhanced CT (CECT), and MRI were performed before and early after onset of TKI treatment (range 8-18 days). Early response was categorized according to mRECIST (CT), the Choi criteria (CECT), and PERCIST (FDG PET/CT). For MRI, volumetry from T2-weighted images and change in apparent diffusion coefficient (ADC) from diffusion-weighted imaging was used. The reference standard for early assessment was the three-month mRECIST evaluation based on CT. At three months, both stable disease (SD) and partial response (PR) were categorized as response. Clinical usefulness was defined as agreement between early and three-month assessment. At the three-month assessment, 91% (32/35) were responders, 37% (13/35) PR, 54% (19/35) SD, and 9% (3/35) had progressive disease (PD). Early assessment correctly predicted three-month response in 93% (27/29) for MRI, 80% (28/35) for PERCIST, 74% (26/35) for Choi, and 23% (8/35) for mRECIST. Six patients had non-FDG-avid tumors. For the FDG-avid tumors, PET/CT correctly predicted three-month response in 97% (28/29). MRI was superior to CECT for early assessment of TKI-treatment response in GIST. If the tumor was FDG-avid, PET and MRI were equally good. Changes in functional parameters were superior to changes in longest tumor diameter (mRECIST).

Early efficacy prediction of nasopharyngeal carcinoma based on 3D-ADC value acquired during radiotherapy: A phase II prospective study.

e18018 Background: Concurrent chemoradiotherapy (CCRT) is the main treatment for locally advanced nasopharyngeal carcinoma (LANPC). The prognosis of the patients with the same stage receiving the same treatment varies greatly. We aimed to investigate the dynamic changes of apparent diffusion coefficient (ADC) map from diffusion weighted MRI (DWI) of primary tumor (PT) and metastatic lymph nodes (LN) for NPC patients during RT process, and analyzed the potential correlations with volume reduction and objective response rate (ORR). Methods: A total of 50 NPC patients treated with CCRT were enrolled in this prospective study. All patients received a planned total dose of 66 to 70Gy in 33 fractions at 5 fractions per week using Image-guided intensity modulated radiotherapy (IGRT). The CCRT protocol was cisplatin (80-100mg/m2) every 3 weeks for 3 cycles. All patients received DWI scan at pre-RT, the 5th and 15th fractions and immediately post-RT on a 3.0T MRI system (b=0, 500, 800s/mm2) system. The ADC values of PT and LN were acquired on ADC map. RECIST1.1criteria was used to evaluate the ORR for both PT and LN. Clinical predictors of complete response (CR) were evaluated using log-rank test. Multivariate analyses were calculated using the logistic regression model. Receiver-operating characteristic (ROC) curve was used to determine the cut-off value of ADC value. P <0.05. Results: After the completion of C CRT, the ORR of the PT was 100% (CR 75%, PR 25%), and that of the LN also reached 100% (CR 52%, PR 48%). Mean ADC increases and volume reductions in PT and LN were observed during RT. In the first stage (from pre-RT to the 5th fraction), the mean ADC increased significantly by 20.78% (PT), 22.96% (LN), while the volumes of PT and LN had minimal changes (PT:18.42cm3vs 16.72cm3, LN: 4.67cm3 vs 4.12cm3). In the second stage (from the 5th fraction to post-RT), the mean ADC increased by 45.58% (PT), 41.2% (LN), the volumes decreased by 86.07% (PT), 61.6% (LN). The increased mean ADC at the first stage had a positive correlation with the volume reduction after RT (r PT=0.32; r LN=0.40). Univariate analysis showed significant differences in the age, the changes of 3D-ADC at the 5th RT and the volume of PT and LN before RT (VPT, VLN) between CR group and PR group(p<0.05), The binary logistic regression analysis demonstrated the ADC changes and the VPT, VLN were predictor of PT and LN efficacy evaluation. ROC analysis suggested the ADC changes had the better performance for PT and LN efficacy evaluation. The cut-off the ADC value changes of PT and LN was 193.52mm2/s (AUC = 0.750, p = 0.008) , 173.80mm2/s (AUC = 0.822, p < 0.001) respectively. Conclusions: 3D-ADC values of PT and LN increased dramatically during RT for NPC patients. The 3D-ADC value of PT and LN was an independent prognostic factor for NPC patients. Early ADC changes at the 5th fraction might be a new and sensitive biomarker to predict the efficacy for NPC patients.

Diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging after radiation therapy for bone metastases in patients with hepatocellular carcinoma

The objectives of this study were to assess changes in apparent diffusion coefficient (ADC) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters after radiation therapy (RT) for bone metastases from hepatocellular carcinoma (HCC) and to evaluate their prognostic value. This prospective study was approved by the Institutional Review Board. Fourteen patients with HCC underwent RT (30 Gy in 10 fractions once daily) for bone metastases. The ADC and DCE-MRI parameters and the volume of the target lesions were measured before (baseline) and one month after RT (post-RT). The Wilcoxon signed-rank test was used to compare the parameters between the baseline and post-RT MRI. The parameters were compared between patients with or without disease progression in RT fields using the Mann–Whitney test. Intraclass correlation coefficients were used to evaluate the interobserver agreement. The medians of the ADC, rate constant [kep], and volume fraction of the extravascular extracellular matrix [ve] in the baseline and post-RT MRI were 0.67 (range 0.61–0.72) and 0.75 (range 0.63–1.43) (× 10–3 mm2/s) (P = 0.027), 836.33 (range 301.41–1082.32) and 335.80 (range 21.86–741.87) (× 10–3/min) (P = 0.002), and 161.54 (range 128.38–410.13) and 273.99 (range 181.39–1216.95) (× 10–3) (P = 0.027), respectively. The medians of the percent change in the ADC of post-RT MRI in patients with progressive disease and patients without progressive disease were − 1.35 (range − 6.16 to 6.79) and + 46.71 (range 7.71–112.81) (%) (P = 0.011), respectively. The interobserver agreements for all MRI parameters were excellent (intraclass correlation coefficients > 0.8). In conclusion, the ADC, kep, and ve of bone metastases changed significantly after RT. The percentage change in the ADC was closely related to local tumor progression.

Apparent diffusion coefficient agreement and reliability using different region of interest methods for the evaluation of head and neck cancer post chemo-radiotherapy.

Objectives:Post chemoradiotherapy (CRT) interval changes in apparent diffusion coefficient (ADC) have prognostic value in head and neck squamous cell cancer (HNSCC). The impact of using different region of interest (ROI) methods on interobserver agreement and their ability to reliably detect the changes in the ADC values was assessed.Methods:Following ethical approval, 25 patients (mean age 59.5 years, 21 male) with stage 3–4 HNSCC undergoing CRT were recruited for this prospective cohort study. Diffusion weighted MRI (DW-MRI) was performed pre-treatment and at 6 and 12 weeks following CRT. Two radiologists independently delineated ROIs using whole volume (ROIv), largest area (ROIa) or representative area (ROIr) methods at primary tumour (n = 22) and largest nodal (n = 24) locations and recorded the ADCmean. When no clear focus of increased DWI signal was evident at follow-up, a standardised ROI was placed (non-measurable or NM). Bland-Altman plots and interclass correlation coefficient (ICC) were assessed. Paired t-tests evaluated interval changes in pre- and post-treatment ADCmean at each location, which were compared to the smallest detectable difference (SDD).Results:Excellent agreement was obtained for all ROI methods at pre-treatment (ICC 0.94–0.98) and 6-week post-treatment (ICC 0.94–0.98). At 12-week post-treatment, agreement was excellent (ICC 0.91–0.94) apart from ROIr (ICC 0.86) and the NM nodal disease (ICC 0.87). There were significant interval increases in ADCmean between pre-treatment and post-treatment studies, which were greater than the SDD for all ROIs.Conclusions:ADCmean values can be reproducibly obtained in HNSCC using the different ROI techniques on pre- and post-CRT MRI, and this reliably detects the interval changes.

A Rodent Model of Mild Neonatal Hypoxic Ischemic Encephalopathy.

In the brain of full-term newborns, Hypoxic Ischemic Encephalopathy (HIE), a consequence of severe hypoxia and ischemia due to low cardiac output, is frequently observed and results in cerebral injuries with dramatic consequences for life. To investigate the physiopathology of HIE, several animal models have been developed, but none closely replicate human cases, mostly because they are based on a single carotid ligation protocol. In the present study we aimed to develop a novel and more accurate HIE model in juvenile (post-natal days (PND) 14–16) rats. For this, we induced a 9 min hypoxic cardiac arrest (CA) by stopping mechanical ventilation of intubated, ventilated and curarized rats followed by a cardiopulmonary resuscitation. To evaluate the consequences of the CA we performed radiological (cerebral MRI), behavioral (Open Field, Elevated Plus Maze, Fear Conditioning), and histological (Cresyl Violet and Fluoro-Jade B) testing on treated animals. We found that rats in the CA group developed an anxiolytic-like behavioral profile in adulthood without any locomotor impairment, nor memory deficits. However, MRI investigation performed early after CA failed to reveal any change in apparent diffusion coefficient (ADC) in brain tissue (including the hippocampus, striatum, and thalamus), suggesting no massive anatomical lesion had occurred. In contrast, signs of neurodegeneration were found in the Dentate Gyrus and the CA1 region of the hippocampus at day 1 post-CA, suggesting that the anxiolytic-like phenotype observed in adulthood could be related to an abnormal degeneration of this brain region beginning immediately after CA. Thus, our model, despite not representing a severe condition of HIE, nonetheless constitutes a potential model for studying mild, yet persistent and region-specific cerebral injury resulting from an acute oxygen deprivation.

Serial magnetic resonance imaging findings during severe attacks of familial hemiplegic migraine type 2: a case report

Background Hemiplegic migraines represent a heterogeneous disorder with various presentations. Hemiplegic migraines are classified as sporadic or familial based on the presence of family history, but both subtypes have an underlying genetic etiology. Mutations in the ATP1A2 gene are responsible for Familial Hemiplegic type 2 (FHM2) or the sporadic hemiplegic migraine (SHM) counterpart if there is no family history of the disorder. Manifestations include migraine with aura and hemiparesis along with a variety of other symptoms likely dependent upon the specific mutation(s) present.Case presentationWe report the case of an adult man who presented with headache, aphasia, and right-sided weakness. Workup for stroke and various infectious agents was unremarkable during the patient’s extended hospital stay. We emphasize the changes in the Magnetic Resonance Imaging (MRI) over time and the delay from onset of symptoms to MRI changes in Isotropic Diffusion Map (commonly referred to as Diffusion Weighted Imaging (DWI)) as well as Apparent Diffusion Coefficient (ADC).ConclusionsWe provide a brief review of imaging findings correlated with signs/symptoms and specific mutations in the ATP1A2 gene reported in the literature. Description of the various mutations and consequential presentations may assist neurologists in identifying cases of Hemiplegic Migraine, which may include transient changes in ADC and DWI imaging throughout the course of an attack.

Diffusion-weighted imaging in differentiating mid-course responders to chemotherapy for long-bone osteosarcoma compared to the histologic response: an update

BackgroundDiffusion-weighted imaging (DWI) has been described to correlate with tumoural necrosis in response to preoperative chemotherapy for osteosarcoma.ObjectiveTo assess the accuracy of DWI in evaluating the response to neoadjuvant chemotherapy at the mid-course treatment of long-bone osteosarcoma and in predicting survival.Materials and methodsWe conducted a prospective single-centre study over a continuous period of 11 years. Consecutive patients younger than 20 years treated with a neoadjuvant regimen for peripheral conventional osteosarcoma were eligible for inclusion. Magnetic resonance imaging (MRI) with DWI was performed at diagnosis, and mid- and end-course chemotherapy with mean apparent diffusion coefficients (ADC) calculated at each time point. A percentage less than or equal to 10% of the viable residual tissue at the histological analysis of the surgical specimen was defined as a good responder to chemotherapy. Survival comparisons were calculated using the Kaplan-Meier method. Uni- and multivariate analyses with ADC change were performed by Cox modelling. This is an expansion and update of our previous work.ResultsTwenty-six patients between the ages of 4.8 and 19.6 years were included, of whom 14 were good responders. At mid-course chemotherapy, good responders had significantly higher mean ADC values (P=0.046) and a higher increase in ADC (P=0.015) than poor responders. The ADC change from diagnosis to mid-course MRI did not appear to be a prognosticator of survival and did not impact survival rates of both groups.ConclusionDWI at mid-course preoperative chemotherapy for osteosarcoma should be considered to evaluate the degree of histological necrosis and to predict survival. The anticipation of a response to neoadjuvant treatment by DWI may have potential implications on preoperative management.

Quantitative assessment of age-related changes in the mandibular bone marrow using apparent coefficient value.

The purpose of this study was to investigate the age-related changes in apparent diffusion coefficient (ADC) values of the mandibular bone marrow using diffusion-weighted imaging (DWI). This retrospective cohort study comprised all patients who underwent pantomography and magnetic resonance imaging (MRI) between April 2018 and November 2020 at our institution. A total of 351 participants (140 men, 211 women), aged 15-89years (mean age 46.01years), were included in the study. Spearman's correlation coefficients were calculated using age groups as the criterion variable and the ADC values as the explanatory variables. P < 0.05 was considered statistically significant. The mean ADC value for all age groups was 0.91 ± 0.18 in men and 0.86 ± 0.16 in women (p = 0.016). There was a significant negative correlation between age and the ADC values in each sex group (p < 0.001). This study demonstrates that the normal ADC values of the mandibular bone marrow show significant negative correlation with increasing age. These findings will be useful in the diagnosis of bone marrow diseases.

Dynamic Three-Dimensional ADC Changes of Parotid Glands During Radiotherapy Predict the Salivary Secretary Function in Patients With Head and Neck Squamous Carcinoma.

ObjectiveTo investigate the changes of three-dimensional apparent diffusion coefficient (3D-ADC) of bilateral parotid glands during radiotherapy for head and neck squamous cell carcinoma (HNSCC) patients and explore the correlations with the radiation dose, volume reduction of parotid gland and the salivary secretary function.Materials and Methods60 HNSCC were retrospectively collected in Sichuan cancer hospital. The patients were all received diffusion-weighted imaging (DWI) scan at pre-radiation, the 15th radiation, the 25th radiation and completion of radiation. Dynamic 3D-ADC were measured in different lobes of parotid glands (P1: deep lobe of ipsilateral; P2: superficial lobe of ipsilateral; P3: deep lobe of contralateral; P4: superficial lobe of contralateral), and the 3D-ADC of spinal cord were also recorded. Chewing stimulates test, radionuclide scan and RTOG criteria were recorded to evaluate the salivary secretary function. Pearson analysis was used to assess the correlation between 3D-ADC value, radiation dose, volume change, and salivary secretary function.ResultsThe mean 3D-ADC of parotid glands increased. It began to change at the 15th radiation and the mostly increased in P1. However, there was no change for the maximum and minimum 3D-ADC. The 3D-ADC values of spinal cord changes were almost invisible (ratio ≤ 0.03 ± 0.01). The mean 3D-ADC was negatively correlated with the salivary secretary function (r=-0.72) and volume reduction of different lobes of parotid glands (r1=-0.64; r2=-0.61; r3=-0.57; r4=-0.49), but it was positively correlated with the delivered dose (r1 = 0.73; r2 = 0.69; r3 = 0.65; r4 = 0.78).ConclusionDynamic 3D-ADC changes might be a new and early indicator to predict and evaluate the secretary function of parotid glands during radiotherapy.

Semi-Automated Segmentation of Bone Metastases from Whole-Body MRI: Reproducibility of Apparent Diffusion Coefficient Measurements.

Using semi-automated software simplifies quantitative analysis of the visible burden of disease on whole-body MRI diffusion-weighted images. To establish the intra- and inter-observer reproducibility of apparent diffusion coefficient (ADC) measures, we retrospectively analyzed data from 20 patients with bone metastases from breast (BCa; n = 10; aged 62.3 ± 14.8) or prostate cancer (PCa; n = 10; aged 67.4 ± 9.0) who had undergone examinations at two timepoints, before and after hormone-therapy. Four independent observers processed all images twice, first segmenting the entire skeleton on diffusion-weighted images, and then isolating bone metastases via ADC histogram thresholding (ADC: 650–1400 µm2/s). Dice Similarity, Bland-Altman method, and Intraclass Correlation Coefficient were used to assess reproducibility. Inter-observer Dice similarity was moderate (0.71) for women with BCa and poor (0.40) for men with PCa. Nonetheless, the limits of agreement of the mean ADC were just ±6% for women with BCa and ±10% for men with PCa (mean ADCs: 941 and 999 µm2/s, respectively). Inter-observer Intraclass Correlation Coefficients of the ADC histogram parameters were consistently greater in women with BCa than in men with PCa. While scope remains for improving consistency of the volume segmented, the observer-dependent variability measured in this study was appropriate to distinguish the clinically meaningful changes of ADC observed in patients responding to therapy, as changes of at least 25% are of interest.

Quantitative Whole-Body Diffusion-weighted MRI after One Treatment Cycle for Aggressive Non-Hodgkin Lymphoma Is an Independent Prognostic Factor of Outcome.

To evaluate the prognostic utility of apparent diffusion coefficient (ADC) changes at whole-body diffusion-weighted (WB-DW) MRI after one treatment cycle for aggressive non-Hodgkin lymphoma (NHL) compared with response assessment at interim and end-of-treatment fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT. This was a secondary analysis of a prospective study (ClinicalTrials.gov identifier: NCT01231269) in which participants with aggressive NHL were recruited between March 2011 and April 2015 and underwent WB-DW MRI before and after one cycle of immunochemotherapy. Volunteers were recruited for test-retest WB-DW MRI (ClinicalTrials.gov identifier: NCT01231282) to assess ADC measurement repeatability. Response assessment was based on ADC change after one treatment cycle at WB-DW MRI and Deauville criteria at 18F-FDG PET/CT. To evaluate prognostic factors of disease-free survival (DFS), Kaplan-Meier survival analysis and univariable and multivariable Cox regression were performed; intraclass correlation coefficient (ICC) and mean difference with limits of agreement were calculated to determine inter- and intraobserver repeatability of ADC measurements. Forty-five patients (mean age, 58 years ± 17 [standard deviation]; 31 men) and nine volunteers (mean age, 22 years ± 3; seven men) were enrolled. Median DFS was 48 months (range, 2-48 months). Outcome prediction accuracy was 86.7% (39 of 45), 71.4% (30 of 42), and 73.8% (31 of 42) for WB-DW MRI and interim and end-of-treatment 18F-FDG PET/CT, respectively. WB-DW MRI (hazard ratio [HR], 17.8; P < .001) and interim (HR, 5; P = .008) and end-of-treatment (HR, 4.3; P = .017) 18F-FDG PET/CT were prognostic of DFS. After multivariable analysis, WB-DW MRI remained an independent predictor of outcome (HR, 26.8; P = .002). Intra- and interobserver agreement for ADC measurements were excellent (ICC = 0.85-0.99). Quantitative WB-DW MRI after only one cycle of immunochemotherapy predicts DFS in aggressive NHL and is noninferior to routinely performed interim and end-of-treatment 18F-FDG PET/CT.Keywords: MR-Diffusion Weighted Imaging, Lymphoma, Oncology, Tumor Response, Whole-Body ImagingSupplemental material is available for this article.© RSNA, 2021.

Diffusion weighted imaging in submandibular gland sparing helical tomotherapy for nasopharyngeal carcinoma

PurposeTo verify clinical significance of submandibular gland (SMG)-sparing during helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC) from the perspective of imaging by using diffusion weighted imaging (DWI). Materials and methodsIn this prospective study, 60 NPC patients scheduled for radical SMG-sparing HT were enrolled. All patients underwent DWI examinations prior to HT (pre-HT) and 1, 3, 6, 9, 12 months post HT. Mean apparent diffusion coefficient (ADC) values of bilateral parotid glands (PGs) and submandibular glands (SMGs) were measured. Differences of ADC and changes of ADC pre and pro HT (ΔADC) among SMG-spared, SMG-unspared and PGs were compared and the associations betweenΔADC and variations of patient-rated xerostomia questionnaire summary scores (XQ-sum) were further tested. ResultsADCpost-HT and ΔADCpost-HT of SMG-spared were both much lower than of SMG-unspared and a strong dose–response relationship was detected between mean radiation dose and ΔADC of SMGs. Dynamic change trends of PGs, SMG-spared and SMG-unspared were similar, with initial increase at 1 m-post-HT followed by little change at 3 m-post-HT and then gradual decrease over time. But for SMG-unspared, there was no obvious change of ADC from 6 m-post-HT to 12 m-post-HT. The dynamic change trend of XQ-sum was nearly in line with that of ADC on the whole. And a positive correlation between mean ΔADC1m-post-HT of bilateral SMGs and variation of XQ-sum1m-post-HT in patients with bSMG-unspared were found (r = 0.693, P < 0.001). Multivariate stepwise regression analysis showed that whether spared SMG or not was the only independent predictor correlated to XQ-sumpost-HT at each follow-up timepoint. ConclusionSMG-sparing technique could significantly improve subjective xerostomia post HT in NPC patients from the perspective of imaging.

Predicting the effects of radiotherapy based on diffusion kurtosis imaging in a xenograft mouse model of esophageal carcinoma.

The aim of the present study was to assess the predictive value of diffusion kurtosis imaging (DKI) on the effects of radiotherapy in a xenograft model of esophageal cancer. A total of 40 tumor-bearing mice, established by injection of Eca-109 cells in nude mice, were used. The experimental group (n=24) received a single dose of 15 Gy (6 MV by X-ray), and the control group (n=16) did not receive any treatment. Tumor volume, apparent diffusion coefficient (ADC), mean kurtosis (MK) and mean diffusivity (MD) of the two groups were compared, and the expression of aquaporin (AQP) 3 and necrosis ratio at matched time points in xenografts were also observed. There was a significant difference between the two groups from the 7th day of radiotherapy onwards; the xenograft volume of the experimental group was significantly smaller compared with the control group (P<0.05). On the 3rd day, the ADC and MD of the experimental group was significantly higher compared with the control group, and MK was significantly lower compared with the control group (P<0.05). On the 3rd day, AQP3 expression in the experimental group was lower compared with the control group, and the proportion of necrotic cells was higher compared with the control group (P<0.05). Single large fraction dose radiotherapy inhibited the growth of a xenografted esophageal tumor. Changes in ADC, MK and MD were observed prior to morphological changes in the tumor. The change in AQP3 expression and necrosis ratio was in also agreement with the DKI parameters assessed. DKI may thus provide early predictive ability on the effect of radiotherapy in esophageal carcinoma.

Diffusion kurtosis imaging assessment of the response to radiotherapy in a VX2 bone tumor model: an animal study.

Neoadjuvant radiotherapy plays a vital role in the treatment of malignant bone tumors, and non-invasive imaging methods are needed to evaluate the response to treatment. To assess the value of diffusion kurtosis imaging (DKI) for monitoring early response to radiotherapy in malignant bone tumors. Treatment response was evaluated in a rabbit VX2 bone tumor model (n = 35) using magnetic resonance imaging (MRI), DKI, and histopathologic examinations. Subjects were divided into three groups: pre-treatment, post-treatment, and control groups. The post-treatment group was subclassified into good response and poor response groups according to the results of histopathologic examination. Apparent diffusion coefficient (ADC) and DKI parameters (mean diffusion coefficient [MD] and mean kurtosis [MK]) were recorded. The relationship between ADC, DKI parameters, and histopathologic changes after radiotherapy was determined using Pearson's correlation coefficient. The diagnostic performance of these parameters was assessed using receiver operating characteristic analysis. MD in the good response group was higher after treatment than before treatment (P < 0.001) and higher than that in the poor response group (P = 0.009). MD was highly correlated with tumor cell density and apoptosis rate (r = -0.771, P < 0.001 and r = 0.625, P < 0.001, respectively). MD was superior to other parameters for determining the curative effect of radiotherapy, with a sensitivity of 75.0%, specificity of 100.0%, and area under the curve of 0.917 (P < 0.001). The correlations between MD, tumor cell density, and apoptosis suggest that MD could be useful for assessing the early response to radiotherapy in rabbit VX2 malignant bone tumors.

Repeatability and reproducibility of ADC measurements: a prospective multicenter whole-body-MRI study.

Multicenter oncology trials increasingly include MRI examinations with apparent diffusion coefficient (ADC) quantification for lesion characterization and follow-up. However, the repeatability and reproducibility (R&R) limits above which a true change in ADC can be considered relevant are poorly defined. This study assessed these limits in a standardized whole-body (WB)-MRI protocol. A prospective, multicenter study was performed at three centers equipped with the same 3.0-T scanners to test a WB-MRI protocol including diffusion-weighted imaging (DWI). Eight healthy volunteers per center were enrolled to undergo test and retest examinations in the same center and a third examination in another center. ADC variability was assessed in multiple organs by two readers using two-way mixed ANOVA, Bland-Altman plots, coefficient of variation (CoV), and the upper limit of the 95% CI on repeatability (RC) and reproducibility (RDC) coefficients. CoV of ADC was not influenced by other factors (center, reader) than the organ. Based on the upper limit of the 95% CI on RC and RDC (from both readers), a change in ADC in an individual patient must be superior to 12% (cerebrum white matter), 16% (paraspinal muscle), 22% (renal cortex), 26% (central and peripheral zones of the prostate), 29% (renal medulla), 35% (liver), 45% (spleen), 50% (posterior iliac crest), 66% (L5 vertebra), 68% (femur), and 94% (acetabulum) to be significant. This study proposes R&R limits above which ADC changes can be considered as a reliable quantitative endpoint to assess disease or treatment-related changes in the tissue microstructure in the setting of multicenter WB-MRI trials. • The present study showed the range of R&R of ADC in WB-MRI that may be achieved in a multicenter framework when a standardized protocol is deployed. • R&R was not influenced by the site of acquisition of DW images. • Clinically significant changes in ADC measured in a multicenter WB-MRI protocol performed with the same type of MRI scanner must be superior to 12% (cerebrum white matter), 16% (paraspinal muscle), 22% (renal cortex), 26% (central zone and peripheral zone of prostate), 29% (renal medulla), 35% (liver), 45% (spleen), 50% (posterior iliac crest), 66% (L5 vertebra), 68% (femur), and 94% (acetabulum) to be detected with a 95% confidence level.

Biomarkers for site-specific response to neoadjuvant chemotherapy in epithelial ovarian cancer: relating MRI changes to tumour cell load and necrosis

BackgroundDiffusion-weighted magnetic resonance imaging (DW-MRI) potentially interrogates site-specific response to neoadjuvant chemotherapy (NAC) in epithelial ovarian cancer (EOC).MethodsParticipants with newly diagnosed EOC due for platinum-based chemotherapy and interval debulking surgery were recruited prospectively in a multicentre study (n = 47 participants). Apparent diffusion coefficient (ADC) and solid tumour volume (up to 10 lesions per participant) were obtained from DW-MRI before and after NAC (including double-baseline for repeatability assessment in n = 19). Anatomically matched lesions were analysed after surgical excision (65 lesions obtained from 25 participants). A trained algorithm determined tumour cell fraction, percentage tumour and percentage necrosis on histology. Whole-lesion post-NAC ADC and pre/post-NAC ADC changes were compared with histological metrics (residual tumour/necrosis) for each tumour site (ovarian, omental, peritoneal, lymph node).ResultsTumour volume reduced at all sites after NAC. ADC increased between pre- and post-NAC measurements. Post-NAC ADC correlated negatively with tumour cell fraction. Pre/post-NAC changes in ADC correlated positively with percentage necrosis. Significant correlations were driven by peritoneal lesions.ConclusionsFollowing NAC in EOC, the ADC (measured using DW-MRI) increases differentially at disease sites despite similar tumour shrinkage, making its utility site-specific. After NAC, ADC correlates negatively with tumour cell fraction; change in ADC correlates positively with percentage necrosis.Clinical trial registrationClinicalTrials.gov NCT01505829.

Intravoxel incoherent motion as a tool to detect early microstructural changes in meningiomas treated with proton therapy.

To assess early microstructural changes of meningiomas treated with proton therapy through quantitative analysis of intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI) parameters. Seventeen subjects with meningiomas that were eligible for proton therapy treatment were retrospectively enrolled. Each subject underwent a magnetic resonance imaging (MRI) including DWI sequences and IVIM assessments at baseline, immediately before the 1st (t0), 10th (t10), 20th (t20), and 30th (t30) treatment fraction and at follow-up. Manual tumor contours were drawn on T2-weighted images by two expert neuroradiologists and then rigidly registered to DWI images. Median values of the apparent diffusion coefficient (ADC), true diffusion (D), pseudo-diffusion (D*), and perfusion fraction (f) were extracted at all timepoints. Statistical analysis was performed using the pairwise Wilcoxon test. Statistically significant differences from baseline to follow-up were found for ADC, D, and D* values, with a progressive increase in ADC and D in conjunction with a progressive decrease in D*. MRI during treatment showed statistically significant differences in D values between t0 and t20 (p= 0.03) and t0 and t30 (p= 0.02), and for ADC values between t0 and t20 (p= 0.04), t10 and t20 (p = 0.02), and t10 and t30 (p= 0.035). Subjects that showed a volume reduction greater than 15% of the baseline tumor size at follow-up showed early D changes, whereas ADC changes were not statistically significant. IVIM appears to be a useful tool for detecting early microstructural changes within meningiomas treated with proton therapy and may potentially be able to predict tumor response.

Evaluation of Brainstem Subcortical Auditory Pathways with Diffusion Tensor Imaging After Gamma Knife Radiosurgery in Intracanalicular Vestibular Schwannoma.

ObjectiveTo investigate changes in DTI (Diffusion Tensor Imaging) parameters in brainstem subcortical auditory pathways after Gamma Knife Radiosurgery (GKR) in patients with intracanalicular vestibular schwannoma (ICVS) and to analyze the relationship between tumor volume and ADC (apparent diffusion coefficient) and FA (fractional anisotropy) values.MethodSeventeen patients with ICVS were evaluated before and after GKR. ADC and FA values of the lateral lemniscus (LL) and inferior colliculus (IC) and tumor volume were calculated. Patients who responded to GKR were classified as Group 1 and those who did not respond adequately as Group 2. The relationship between ADC and FA values and changes in tumor volume were analyzed.ResultsTumor volume significantly decreased after GKR. ADC values obtained from the tumor increased after GKR (p:0.002). There was no significant difference in LL and IC before and after GKR in terms of FA and ADC values (n:17). There was a positive correlation between response to treatment and contralateral LL ADC values after GKR (p=0.005, r:0.652). There was a negative correlation between contralateral IC FA values after GKR and response to treatment (p=0.017, r: -0.568). There was a significant difference between Groups 1 and 2 in regards to contralateral LL ADC (p=0.03) and IC FA values (p=0.017).ConclusionSince the cochlear nerve and subcortical auditory pathways have low regeneration potential after nerve damage, ADC and FA changes in LL and IC may be explained with the presence of intracanalicular tumors prior to GKR. Since GKR does not cause additional damage to the subcortical auditory pathways at the brainstem level, we think that GKR is a noninvasive treatment method that can be used safely in patients with ICVS.

Extra pulmonary boosting in chronic obstructive pulmonary disease

Background Promotion of central control of respiration might contribute in minimization of chronic obstructive lung disease disability. Objectives Our study was done to evaluate the effect of oral supplementation of piracetam tablets in low dose (400 mg twice daily) versus high dose (1200 mg twice daily) in patients with chronic obstructive pulmonary disease grade IV with type II respiratory failure, on respiratory parameters (spirometric, respiratory muscle strength, and diaphragmatic echographic measurements; velocity and excursion), in addition to neuropsychiatric parameters (cognitive functions and brain changes with MRI). Patients and methods This randomized controlled study was conducted on 126 patients who were subjected to oral piracetam and classified into group A (42 patients received 800 mg daily for 3 months), group B (44 patients received 2400 mg daily for 3 months) for 3 months, and group C (40 patients) as a control group. Pulmonary evaluation, by spirometry and respiratory muscle study by Pimax, Pemax, Sniff test, and diaphragmatic echography, was conducted in addition to neuropsychiatric evaluation by Alzheimer disease 8 cognitive score assessment and brain MRI. Results Total pulmonary fractional functional progress of piracetam was higher in group B (28.12%) than group A (23.27%) and the control group (5.68%). On the contrary, neuropsychiatric fractional functional progress was higher in group B (29.11%) than group A (15.7%), and lastly, the control group (&lt;1%). Conclusion Oral piracetam demonstrated enhanced spirometric parameters and improved cognition with low dose, but with high dose, it enhanced both spirometric and respiratory muscle strength and cognitive parameters with brain MRI and apparent diffusion coefficient changes.

Irreversible electroporation ablation overcomes tumor-associated immunosuppression to improve the efficacy of DC vaccination in a mice model of pancreatic cancer

ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is associated with highly immunosuppressive tumor microenvironment (TME) that can limit the efficacy of dendritic cell (DC) vaccine immunotherapy. Irreversible electroporation (IRE) is a local ablation approach. Herein, we test the hypothesis that IRE ablation can overcome TME immunosuppression to improve the efficacy of DC vaccination using KrasLSL-G12D-p53LSL-R172H-Pdx-1-Cre (KPC) orthotopic mouse model of PDAC. The median survival for mice treated with the combined IRE and DC vaccination was 77 days compared with sham control (35 days), DC vaccination (49 days), and IRE (44 days) groups (P = .006). Thirty-six percent of the mice treated with combination IRE and DC vaccination were still survival at the end of the study period (90 days) without visible tumor. The changes of tumor apparent diffusion coefficient (ΔADC) were higher in mice treated with combination IRE and DC vaccination than that of other groups (all P < .001); tumor ΔADC value positively correlated with tumor fibrosis fraction (R = 0.707, P < .001). IRE induced immunogenic cell death and alleviation of immunosuppressive components in PDAC TME when combined with DC vaccination, including increased tumor infiltration of CD8+ T cells and Granzyme B+ cells (P = .001, and P = .007, respectively). Our data show that IRE ablation can overcome TME immunosuppression to improve the efficacy of DC vaccination in PDAC. Combination IRE ablation and DC vaccination may enhance therapeutic efficacy for PDAC.