In vivo multiparametric magnetic resonance imaging study for differentiating the severity of hepatic warm ischemia-reperfusion injury in a rabbit model

ObjectivesTo assess the value of multiparametric magnetic resonance imaging including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI) and blood oxygen level dependent (BOLD) MRI in differentiating the severity of hepatic warm ischemia-reperfusion injury (WIRI) in a rabbit model.MethodsFifty rabbits were randomly divided into a sham-operation group and four test groups (n = 10 for each group) according to different hepatic warm ischemia times. IVIM, DTI and BOLD MRI were performed on a 3 T MR scanner with 11 b values (0 to 800 s/mm²), 2 b values (0 and 500 s/mm²) on 12 diffusion directions, multiple-echo gradient echo (GRE) sequences (TR/TE, 75/2.57–24.25 ms), respectively. IVIM, DTI and BOLD MRI parameters, hepatic biochemical and histopathological parameters were compared. Pearson and Spearman correlation methods were performed to assess the correlation between these MRI parameters and laboratory parameters. Furthermore, receiver operating characteristic (ROC) curves were compiled to determine diagnostic efficacies.ResultsTrue diffusion (Dslow), pseudodiffusion (Dfast), perfusion fraction (PF), mean diffusivity (MD) significantly decreased, while R2* significantly increased with prolonged warm ischemia times, and significant differences were found in all of biochemical and histopathological parameters (all P < 0.05). Dslow, PF, and R2* correlated significantly with all of biochemical and histopathological parameters (all |r| = 0.381–0.746, all P < 0.05). ROC analysis showed that the area under the ROC curve (AUC) of IVIM across hepatic WIRI groups was the largest among IVIM, DTI and BOLD.ConclusionsMultiparametric MRI may be helpful with characterization of early changes and determination of severity of hepatic WIRI in a rabbit model.     

Cardiac MRI for the prognostication of heart failure with preserved ejection fraction: A systematic review and meta-analysis

BackgroundCardiac magnetic resonance imaging (MRI) is emerging as an important imaging tool in the assessment of heart failure with preserved ejection fraction (HFpEF). This systematic review and meta-analysis aim to synthesise and consolidate the current literature on cardiac MRI for prognostication of HFpEF.Methods designSystematic review and meta-analysis. Data sources: Scopus (PubMed and Embase) for studies published between 2008 and 2019. Eligibility criteria for study selection were studies that evaluated the prognostic role of cardiac MRI in HFpEF. Random effects meta-analyses of the reported hazard ratios (HR) for clinical outcomes was performed.ResultsInitial screening identified 97 studies. From these, only nine (9%) studies met all the criteria. The main cardiac MRI methods that demonstrated association to prognosis in HFpEF included late gadolinium enhancement (LGE) assessment of scar (n = 3), tissue characterisation with T1-mapping (n = 4), myocardial ischaemia (n = 1) and right ventricular dysfunction (RVSD) (n = 1). The pooled HR for all 9 studies was 1.52 (95% CI 1.05–1.99, P < 0.01). Sub-evaluation by cardiac MRI methods revealed varying HRs: LGE (net n = 402, HR = 1.6, 95% CI 0.42–2.78, P = 0.008); T1-mapping (n = 1623, HR = 1.25, 95% CI 0.891–1.60, P < 0.001); myocardial ischaemia or RVSD (n = 325, HR = 3.19, 95% CI 0.30–6.08, P = 0.03).ConclusionThis meta-analysis demonstrates that multiparametric cardiac MRI has value in prognostication of patients with HFpEF. HFpEF patients with a detectable scar on LGE, fibrosis on T1-mapping, myocardial ischaemia or RVSD appear to have a worse prognosis.PROSPERO registration numberCRD42020187228.     

Prediction of survival and progression in glioblastoma patients using temporal perfusion changes during radiochemotherapy

BackgroundThe aim of this study was to investigate changes in structural magnetic resonance imaging (MRI) according to the RANO criteria and perfusion- and permeability related metrics derived from dynamic contrast-enhanced MRI (DCE) and dynamic susceptibility contrast MRI (DSC) during radiochemotherapy for prediction of progression and survival in glioblastoma.MethodsTwenty-three glioblastoma patients underwent biweekly structural and perfusion MRI before, during, and two weeks after a six weeks course of radiochemotherapy. Temporal trends of tumor volume and the perfusion-derived parameters cerebral blood volume (CBV) and blood flow (CBF) from DSC and DCE, in addition to contrast agent capillary transfer constant (K^trans) from DCE, were assessed. The patients were separated in two groups by median survival and differences between the two groups explored. Clinical- and MRI metrics were investigated using univariate and multivariate survival analysis and a predictive survival index was generated.ResultsMedian survival was 19.2 months. A significant decrease in contrast-enhancing tumor size and CBV and CBF in both DCE- and DSC-derived parameters was seen during and two weeks past radiochemotherapy (p < 0.05). A 10%/30% increase in K^trans/CBF two weeks after finishing radiochemotherapy resulted in significant shorter survival (13.9/16.8 vs. 31.5/33.1 months; p < 0.05). Multivariate analysis revealed an index using change in K^trans and relative CBV from DSC significantly corresponding with survival time in months (r² = 0.843; p < 0.001).ConclusionsSignificant temporal changes are evident during radiochemotherapy in tumor size (after two weeks) and perfusion-weighted MRI-derived parameters (after four weeks) in glioblastoma patients. While DCE-based metrics showed most promise for early survival prediction, a multiparametric combination of both DCE- and DSC-derived metrics gave additional information.     

Transplantation of bone-marrow-derived cells into a nerve guide resulted in transdifferentiation into Schwann cells and effective regeneration of transected mouse sciatic nerve

Peripheral nerves possess the capacity of self-regeneration after traumatic injury. Nevertheless, the functional outcome after peripheral-nerve regeneration is often poor, especially if the nerve injuries occur far from their targets. Aiming to optimize axon regeneration, we grafted bone-marrow-derived cells (BMDCs) into a collagen-tube nerve guide after transection of the mouse sciatic nerve. The control group received only the culture medium. Motor function was tested at 2, 4, and 6 weeks after surgery, using the sciatic functional index (SFI), and showed that functional recovery was significantly improved in animals that received the cell grafts. After 6 weeks, the mice were anesthetized, perfused transcardially, and the sciatic nerves were dissected and processed for transmission electron microscopy and light microscopy. The proximal and distal segments of the nerves were compared, to address the question of improvement in growth rate; the results revealed a maintenance and increase of nerve regeneration for both myelinated and non-myelinated fibers in distal segments of the experimental group. Also, quantitative analysis of the distal region of the regenerating nerves showed that the numbers of myelinated fibers, Schwann cells (SCs) and g-ratio were significantly increased in the experimental group compared to the control group. The transdifferentiation of BMDCs into Schwann cells was confirmed by double labeling with S100/and Hoechst staining. Our data suggest that BMDCs transplanted into a nerve guide can differentiate into SCs, and improve the growth rate of nerve fibers and motor function in a transected sciatic-nerve model.     

Associations between histogram analysis parameters derived from dynamic-contrast enhanced MRI and PD L1-expression in head and neck squamous cell carcinomas. A preliminary study

PurposeProgrammed death 1 ligand (PD-L 1) plays an essential role in oncology. It might be crucial to predict its expression non-invasively by imaging. Dynamic-contrast enhanced MRI (DCE MRI) is one of the important imaging modalities in head and neck squamous cell cancer (HNSCC). The aim of the present study was to analyze possible associations between histogram analysis parameters of DCE MRI and PD-L 1 expression in HNSCCMethodsOverall, 26 patients with primary HNSCC of different localizations were involved in the study. DCE MRI was obtained on a 3 T MRI and analyzed with a whole lesion measurement using a histogram approach. PD-L 1 expression was estimated on bioptic samples before any form of treatment using 3 scores (Tumor positive score (TPS), Immune cell score (ICS) and Combined positive score (CPS)).ResultsCPS correlated with mode derived from Ktrans (r = 0.40, p = .04). Also CPS correlated with P90 derived from Kep (r = 0.40, p = .04). ICS correlated with the maximum derived from Kep (r = 0.41, p = .03) and entropy derived from Kep (r = 0.43, p = .02). There were no associations between DCE MRI parameters and TPS.ConclusionKtrans and Kep related histogram analysis parameters derived from DCE MRI correlated moderately with PD-L 1 expression of immune cells in HNSCC.     

Group delay method for MRI aortic pulse wave velocity measurements in clinical protocols with low temporal resolution: Validation in a heterogeneous cohort

BackgroundMRI assessment of aortic pulse wave velocity (PWV) helps predict the risk of vascular events, but the recommended phase contrast sampling rate is faster than what is utilized in most clinical sequences. There are many existing MRI databases obtained for assessment of cardiac output using lower temporal frequency sampling where information might be obtained about aortic stiffness (PWV). In this work, we sought to evaluate whether the Group Delay (GD) method can generate a reproducible measure of stiffness and describe expected age-related stiffening of the aortic arch using lower sampling rates in standard clinical sequences.MethodsPhase contrast (PC) MRI was obtained on the ascending and descending aortic arch in a heterogeneous adult cohort (n = 23; 9 women) spanning over a wide range of ages (ages 24–89, mean 49.4 ± 18.4). Data was collected with standard cardiac MRI protocols for cardiac output evaluation (repetition time = 7.8 ms, views-per-segment = 4, encoding velocity = 200 cm/s). Pulse wave transit times (TT) were computed using the GD method, two other validated automated approaches (cross correlation TT Algorithm by Gaddum and Segment by Medviso), and the manual tangent method. Pressure waveforms from tonometry and flow waveforms from PC MRI were used to assess wave reflections.ResultsGroup Delay and TT-Algorithm showed significant and high retest reproducibility (r = 0.86 for both) as well as high PWV correlation with age (r = 0.93, P-value < 0.00005 and r = 0.96, P-value < 0.00005 respectively) and with each other (r = 0.94, P-value < 0.00001, RMSE = 0.94 m/s). Arbitrary altering of the image acquisition trigger in the GD method introduced error of 10%–13%, but the TT-algorithm error range was 11%–25%.ConclusionGroup Delay enables reproducible assessment of transit time to derive PWV from low temporal resolution clinical cardiac MRI sequences that can also identify age-related stiffening.     

Improved nerve conspicuity with water-weighting and denoising in two-point Dixon magnetic resonance neurography

BackgroundT₂-weighted, two-point Dixon fast-spin-echo (FSE) is an effective technique for magnetic resonance neurography (MRN) that can provide quantitative assessment of muscle denervation. Low signal-to-noise ratio and inadequate fat suppression, however, can impede accurate interpretation.PurposeTo quantify effects of principal component analysis (PCA) denoising on tissue signal intensities and fat fraction (FF) and to determine qualitative image quality improvements from both denoising and water-weighting (WW) algorithms to improve nerve conspicuity and fat suppression.Study typeProspective.SubjectsTwenty-one subjects undergoing MR neurography evaluation (11/10 male/female, mean age = 46.3±13.7 years) with 60 image volumes. Twelve subjects (23 image volumes) were determined to have muscle denervation based on diffusely elevated T₂ signal intensity.Field strength/sequence3 T, 2D, two-point Dixon FSE.AssessmentQualitative assessment included overall image quality, nerve conspicuity, fat suppression, pulsation and ringing artifacts by 3 radiologists separately on a three-point scale (1 = poor, 2 = average, 3 = excellent). Quantitative measurements for FF and signal intensity relative to normal muscle were made for nerve, abnormal muscle and subcutaneous fat.Statistical testsLinear and ordinal regression models were used for quantitative and qualitative comparisons, respectively; 95% confidence intervals (CIs) and p-values for pairwise comparisons were adjusted using the Holm-Bonferroni method. Inter-rater agreement was assessed using Gwet's agreement coefficient (AC₂).ResultsSimulations showed PCA-denoising reduced FF error from 2.0% to 1.0%, and from 7.6% to 3.1% at noise levels of 10% and 30%, respectively. In human subjects, PCA-denoising did not change signal levels and FF quantitatively. WW decreased fat signal significantly (−83.6%, p < 0.001). Nerve conspicuity was improved by WW (odds ratio, OR = 5.8, p < 0.001). Fat suppression was improved by both PCA (OR = 3.6, p < 0.001) and WW (OR = 2.2, p < 0.001). Overall image quality was improved by PCA + WW (OR = 1.7, p = 0.04).ConclusionsWW and PCA-denoising improved nerve conspicuity and fat suppression in MR neurography. Denoising can potentially provide improved accuracy of FF maps for assessing fat-infiltrated muscle.     

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

ObjectivesLiver 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.MethodsMale 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. DDVD_mean (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.ResultsThe control rats and BDL rats (n = 18) had a liver DDVD_mean 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, D_slow, and D_fast; 0.381 for PF, D_fast, and DDVD_mean; and 0.384 for PF, D_slow, and DDVD_mean.ConclusionA combination of PF, D_slow, and D_fast allows total separation of healthy livers and fibrotic livers and the integration of DDVD improved the separation.     

Correlation analysis of apparent diffusion coefficient value and P53 and Ki-67 expression in esophageal squamous cell carcinoma

PurposesTo investigate the relationship between apparent diffusion coefficient (ADC) value and p53 and ki-67 expression in esophageal squamous cell carcinoma (ESCC) patients.Materials and methodsClinical, pathologic and MRI findings of 55 ESCC patients were retrospectively analyzed. Immunohistochemical assay was used to determine the expression level of p53 and ki-67 in esophageal carcinoma tissues. The correlations between the ADC value (including ADCmax, ADCmean and ADCmin) and p53 and ki-67 expression level were explored.ResultsSignificant differences of the ADCmean values were found between positive and negative expression of p53 and between high and low expression of ki-67 in 55 patients of ESCC (P = 0.008, P = 0.036). Receiver operation characteristic (ROC) curve analysis showed that the cutoff value of ADCmean value with positive expression of p53 was 1.475 × 10⁻³ mm²/s, the area under the curve (AUC) was 0.775, and the sensitivity and specificity were 80.0%, 70.0%, respectively. While the cutoff value for the ADCmean value with high expression of ki-67 was 1.590 × 10⁻³ mm²/s, the AUC was 0.713, and the sensitivity and specificity were 66.7%, 76.5%, respectively. The ADCmean values were significantly negatively correlated with the expression level of p53 and ki-67 (r = −0.403, P = 0.008; r = −0.329, P = 0.036).ConclusionThe ADCmean values of ESCC were related with the expression level of p53 and ki-67 in tumor tissue, which may be served as a non-invasive biological indicator to predict the proliferation of ESCC cells and judge the prognosis of patients.     

Unfolding the long-term pathophysiological processes following an acute inflammatory demyelinating lesion of multiple sclerosis

Background

Acute symptomatic inflammation is a main feature of multiple sclerosis but pathophysiological processes underlying total or partial recovery are poorly understood.

Objective

To characterize in vivo these processes at molecular, structural and functional levels using multimodal MR methods.

Methods

A neuroimaging 3-year follow-up (Weeks 0, 3, 11, 29, 59 and 169) was conducted on a 41-year-old woman presenting at baseline with a large acute demyelinating lesion of multiple sclerosis. Conventional magnetic resonance imaging (MRI), magnetization transfer imaging, diffusion-weighted imaging, functional MRI and magnetic resonance spectroscopy were conducted at 1.5 T.

Results

Patient presenting with subacute left hemiplegia recovered progressively (expended disability status scale 7 to 5.5). The MR exploration demonstrated structural functional and metabolic impairments at baseline. Despite restoration of the blood brain barrier integrity, high lactate levels persisted for several weeks concomitant with glial activation. Slow and progressive structural and metabolic restorations occurred from baseline to W169 (lesion volume −64%; apparent diffusion coefficient −14.7%, magnetization transfer ratio +14%, choline −51%, lipids −78%, N-acetylaspartate +77%) while functionality of the motor system recovered.

Conclusions

Multimodal MRI/MRS evidenced long-term dynamics recovery processes involving tissue repair, glial activation, recovery of neuronal function and functional systems. This may impact on customized rehabilitation strategies generally focused on the first months following the onset of symptoms.     

Should abbreviated breast MRI be compliant with American College of Radiology requirements for MRI accreditation?

ObjectiveTo evaluate non-inferiority and diagnostic performance of an American College of Radiology compliant abbreviated MRI protocol (AB-MRI) compared with standard-of-care breast MRI (SOC-BMRI) in patients with increased breast cancer risk.Material and methodsWomen with increased lifetime breast cancer risk by American Cancer Society guidelines underwent breast MRI at a single institution between October 2015 and February 2018. AB-MRI was acquired at 3.0 T with T2-weighted extended fast spin echo triple-echo Dixon and pre- and post-contrast 3D dual-echo fast spoiled gradient echo two-point Dixon sequences with an 8-channel breast coil 1–7 days after SOC-BMRI. Three readers independently reviewed AB-MRI and assigned BI-RADS categories for maximum intensity projection images (AB1), dynamic contrast-enhanced (DCE) images (AB2), and DCE and non-contrast T2 and fat-only images (AB3). These scores were compared to those from SOC-BMRI.ResultsCancer yield was 14 per 1000 (women-years) in 73 women aged 26–75 years (mean 53.5 years). AB-MRI acquisition times (mean 9.63 min) and table times (mean 15.07 min) were significantly shorter than those of SOC-BMRI (means 19.46 and 36.3 min, respectively) (p < .001). Accuracy, sensitivity, specificity, and positive and negative predictive values were identical for AB3 and SOC-BMRI (93%, 100%, 93%, 16.7%, and 100%, respectively). AB-MRI with AB1 and AB2 had significantly lower specificity (AB1 = 73.6%, AB2 = 77.8%), positive predictive values (AB1 = 5%, AB2 = 5.9%), and accuracy (AB1 = 74%, AB2 = 78%) than those of SOC-BMRI (p = .002 for AB1, p = .01 for AB2).ConclusionAB-MRI was acquired significantly faster than SOC-BMRI and its diagnostic performance was non-inferior. Inclusion of T2 and fat-only images was necessary to achieve non-inferiority by multireader evaluation.     

Alterations of the optic pathway between unilateral and bilateral optic nerve damage in multiple sclerosis as revealed by the combined use of advanced diffusion kurtosis imaging and visual evoked potentials

ObjectivesWe investigated changes in the optic tract and optic radiation in patients with multiple sclerosis (MS) by comparing unilateral and bilateral optic nerve damage assessed based on visual evoked potentials (VEPs) using advanced diffusion MR metrics.MethodsIn 21 MS patients, diffusion MRI was performed. Maps of fractional anisotropy, apparent diffusion coefficient (ADC), and mean kurtosis (MK) were computed. On the basis of the P100 latency in VEPs, the MS patients were divided into three groups: bilateral (n = 7), unilateral (n = 7), and no abnormality (n = 7). Their optic tracts and optic radiations were analyzed with diffusion MRI-based fiber tracking. We also investigated the correlations between diffusion parameters and VEPs (n = 21).ResultsIn the optic tract, the diffusion changes in each of the three groups showed step-like changes. The diffusion changes in the optic radiations of the unilateral group were similar to those in the normal VEP group. Only the bilateral group showed significantly higher ADC and lower MK relative to the other two groups (P < 0.05, Steel–Dwass multiple-comparison test). A significant positive correlation between VEP latency and ADC and a significant negative correlation between VEP latency and MK were observed (P < 0.01, Spearman's correction).ConclusionsWe first evaluated the relationship between VEPs and DKI and concluded that the lateral geniculate nucleus may compensate for unilateral damage in the pre-geniculate optic pathway via neural plasticity.     

Histogram parameters derived from T1 and T2 weighted images correlate with tumor infiltrating lymphocytes and tumor-stroma ratio in head and neck squamous cell cancer

PurposeThe present study used histogram analysis values derived from T1- and T2- weighted (w) images to elucidate possible associations with Tumor-infiltrating lymphocytes (TIL) and Vimentin expression in head and neck squamous cell cancer (HNSCC).Materials and methodsOverall, 28 patients (n = 8 female patient, 28.6%) with primary HNSCC of different localizations were involved in the study. Magnetic resonance imaging (MRI) was obtained on a 3 T MRI. The images were analyzed with a whole lesion measurement using a histogram approach. TIL- and vimentin-expression was calculated on biopsy samples before any form of treatment.ResultsSeveral T1-derived parameters correlated with the expression of TIL within the stroma compartment: mean (r = 0.42, p = 0.025), p10 (r = 0.50, p = 0.007), p25 (r = 0.42, p = 0.025), median (r = 0.39, p = 0.036), and mode (r = 0.39, p = 0.04). No T2-derived parameter correlated with the TIL within the stroma compartment. Several T2-derived parameters correlated with the expression of TIL within the tumor compartment: mean (r = −0.52, p = 0.004), max (r = −0.43, p = 0.02), p10 (r = −0.38, p = 0.04), p25 (r = −0.53, p = 0.004), p75 (r = −0.52, p = 0.004), p90 (r = −0.48, p = 0.009), median (r = −0.52, p = 0.004), mode (r = −0.40, p = 0.03). Kurtosis derived from T2w images had significant higher values in tumor-rich tumors, compared to stroma-rich tumors, (mean 5.5 ± 0.5 versus 4.2 ± 1.2, p = 0.028).ConclusionsHistogram analysis parameters derived from T1w and T2w images might be able to reflect tumor compartments and TIL expression in HNSCC.     

Quantitative diffusion-weighted imaging and dynamic contrast-enhanced MR imaging for assessment of tumor aggressiveness in prostate cancer at 3T

PurposeTo compare diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MR imaging (DCE-MRI) for characterization of prostate cancer (PC).Methods104 PC patients who underwent prostate multiparametric MRI at 3T including DWI and DCE-MRI before MRI-guided biopsy or radical prostatectomy. Apparent diffusion coefficient (ADC) with histogram analysis (mean, 0–25th percentile, skewness, and kurtosis), intravoxel incoherent motion model including D and f; stretched exponential model including distributed diffusion coefficient (DDC) and a; and permeability parameters including K^trans, K_ep, and V_e were obtained from a region of interest placed on the dominant tumor of each patient.ResultsADC_mean, ADC_0–25, D, DDC, and V_e were significantly lower and K_ep was significantly higher in GS ≥ 3 + 4 tumors (n = 89) than in GS = 3 + 3 tumors (n = 15), and also in GS ≥ 4 + 3 tumors (n = 57) than in GS ≤ 3 + 4 tumors (n = 47) (P < 0.001 to P = 0.040). f was significantly lower in GS ≥ 4 + 3 tumors than in GS ≤ 3 + 4 tumors (P = 0.022), but there was no significant difference between GS = 3 + 3 tumors and GS ≥ 3 + 4 tumors, or between the remaining metrics in both comparisons. In metrics with area under the curve (AUC) >0.80, there was a significant difference in AUC between ADC_0–25 and D, and DDC for separating GS ≤ 3 + 4 tumors from GS ≥ 4 + 3 tumors (P = 0.040 and P = 0.022, respectively). There were no significant differences between metrics with AUC > 0.80 for separating GS = 3 + 3 tumors from GS ≥ 3 + 4 tumors. ADC_0–25 had the highest correlation with Gleason grade (ρ = −0.625, P < 0.001).ConclusionsDWI and DCE-MRI showed no apparent clinical superiority of non-Gaussian models or permeability MRI over the mono-exponential model for assessment of tumor aggressiveness in PC.     

Axonal outgrowth is associated with increased ERK 1/2 activation but decreased caspase 3 linked cell death in Schwann cells after immediate nerve repair in rats

Background  

Extracellular-signal regulated kinase (ERK1/2) is activated by nerve damage and its activation precedes survival and proliferation of Schwann cells. In contrast, activation of caspase 3, a cysteine protease, is considered as a marker for apoptosis in Schwann cells. In the present study, axonal outgrowth, activation of ERK1/2 by phosphorylation (p-ERK 1/2) and immunoreactivity of cleaved caspase 3 were examined after immediate, delayed, or no repair of transected rat sciatic nerves.     

In vivo detection of distal tumor glycolytic flux stimulated by hepatic ablation in a breast cancer model using hyperpolarized 13C MRI

PurposeHepatic thermal ablation therapy can result in c-Met-mediated off-target stimulation of distal tumor growth. The purpose of this study was to determine if a similar effect on tumor metabolism could be detected in vivo with hyperpolarized ¹³C MRI.Materials and methodsIn this prospective study, female Fisher rats (n = 28, 120–150 g) were implanted with R3230 rat breast adenocarcinoma cells and assigned to either: sham surgery, hepatic radiofrequency ablation (RFA), or hepatic RFA + adjuvant c-Met inhibition with PHA-665752 (RFA + PHA). PHA-665752 was administered at 0.83 mg/kg at 24 h post-RFA. Tumor growth was measured daily. MRI was performed 24 h before and 72 h after treatment on 14 rats, and the conversion of ¹³C-pyruvate into ¹³C-lactate within each tumor was quantified as lactate:pyruvate ratio (LPR). Comparisons of tumor growth and LPR were performed using paired and unpaired t-tests.ResultsHepatic RFA alone resulted in increased growth of the distant tumor compared to sham treatment (0.50 ± 0.13 mm/day versus 0.11 ± 0.07 mm/day; p < 0.001), whereas RFA + PHA (0.06 ± 0.13 mm/day) resulted in no significant change from sham treatment (p = 0.28). A significant increase in LPR was seen following hepatic RFA (+0.016 ± 0.010, p = 0.02), while LPR was unchanged for sham treatment (−0.048 ± 0.051, p = 0.10) or RFA + PHA (0.003 ± 0.041, p = 0.90).ConclusionIn vivo hyperpolarized ¹³C MRI can detect hepatic RFA-induced increase in lactate flux within a distant R3230 tumor, which correlates with increased tumor growth. Adjuvant inhibition of c-Met suppresses these off-target effects, supporting a role for the HGF/c-Met signaling axis in these tumorigenic responses.     

Intravoxel incoherent motion MR imaging analysis for diagnosis of placenta accrete spectrum disorders: A pilot feasibility study

BackgroundPlacenta accreta spectrum (PAS) disorders occur when the placenta adheres abnormally to the uterine myometrium and can have devastating effects on maternal health due to risks of massive postpartum hemorrhage and possible need for emergency hysterectomy. PAS can be difficult to diagnose using routine clinical imaging with ultrasound and structural MRI.ObjectiveTo determine feasibility of using intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) analysis in the diagnosis of the placenta accreta spectrum disorders in pregnant women.MethodsA total of 49 pregnant women were recruited including 14 with pathologically confirmed cases of PAS and 35 health controls without prior cesarean delivery and no suspected PAS by ultrasound. All women underwent diffusion-weighted imaging with an 8 b-value scanning sequence. A semi-automated method for image processing was used, creating a 3D object map, which was then fit to a biexponential signal decay curve for IVIM modeling to determine slow diffusion (D_s), fast diffusion (D_f), and perfusion fraction (P_f).ResultsOur results demonstrated a high degree of model fitting (R² ≥ 0.98), with P_f significantly higher in those with PAS compared to healthy controls (0.451 ± 0.019 versus 0.341 ± 0.022, p = 0.002). By contrast, no statistical difference in the D_f (1.70 × 10⁻² ± 0.38 × 10⁻² versus 1.48 × 10⁻² ± 0.08 × 10⁻² mm²/s, p = 0.211) or D_s (1.34 × 10⁻³ ± 0.10 × 10⁻³ versus 1.45 × 10⁻³ ± 0.007 × 10⁻³ mm²/s, p = 0.215) was found between subjects with PAS and healthy controls.ConclusionsThe use of MRI, and IVIM modeling in particular, may have potential in aiding in the diagnosis of PAS when other imaging modalities are equivocal. However, the widespread use of these techniques will require generation of large normative data sets, consistent sequencing protocols, and streamlined analysis techniques.     

Intravoxel incoherent motion magnetic resonance imaging for breast cancer: A comparison with molecular subtypes and histological grades

PurposeThe purpose of this paper is to investigate whether the IVIM parameters (D, D *, f) helps to determine the molecular subtypes and histological grades of breast cancer.MethodsFifty-one patients with breast cancer were included in the study. All subjects were examined by 3 T Magnetic Resonance Imaging (MRI). Diffusion-weighted imaging (DWI) was undertaken with 16 b-values. IVIM parameters [D (true diffusion coefficient), D* (pseudo-diffusion coefficient), f (perfusion fraction)] were calculated. Histopathological reports were reviewed to histological grade, histological type, and immunohistochemistry. IVIM parameters of tumors with different histological grades and molecular subtypes were compared.ResultsD* and f were significantly different between molecular subtypes (p = 0.019, p = 0.03 respectively). D* and f were higher in the HER-2 group and lower in Triple negative (−) group (D*:36.8 × 10⁻³ ± 5.3 × 10⁻³ mm²/s, f:29.5%, D*:29.8 × 10⁻³ ± 5.6 × 10⁻³ mm²/s, f:21.5% respectively). There was a significant difference in D* and f between HER-2 and Triple (−) subgroups (p = 0,028, p = 0.024, respectively). D* was also significantly different between the HER-2 group and the Luminal group (p = 0,041). While histological grades increase, D and f values tend to decrease, and D* tends to increase. While the Ki-67 index increases, D* and f values tend to increase, and D tend to decrease.ConclusionD* and f values measured with IVIM imaging were useful for assessing breast cancer molecular subtyping. IVIM imaging may be an alternative to breast biopsy for sub-typing of breast cancer with further research.     

Estimating cerebral venous oxygenation in human fetuses with ventriculomegaly using quantitative susceptibility mapping

Rationale and objectivesThe goal of this study was to estimate venous blood oxygen saturation (SvO2) in the superior sagittal sinus (SSS) in fetal brains with ventriculomegaly (VM) using quantitative susceptibility mapping (QSM).Materials and methodsA radiofrequency spoiled gradient echo sequence was used to evaluate data on 19 fetuses with VM (gestational age(GA): median = 29.9 weeks (range 23 to 37.3 weeks)) and 20 healthy fetuses (GA: median = 30.9 (range 22.7 to 38.7 weeks)) at 1.5 T. Susceptibility weighted images encompassing the entire fetal brain were acquired within 1 min. An iterative, geometry constraint-based thresholded k-space division algorithm was used for generating QSM data of the fetal brain. The venous oxygen saturation was calculated using the magnetic susceptibility of the SSS obtained from the QSM data. Mixed-model analysis of variance and interobserver variability assessment were used to analyze the results.ResultsThe median SvO2 values in the entire VM cohort as well as for second and third trimester fetuses (with interquartile range) were: 67.8% (63.2%, 73.6%), 73.1% (69.1%, 77.3%) and 63.8% (59.4%, 68.1%), respectively. The corresponding median SvO2 value in the healthy control group was: 65.3% (58.3%, 68.2%), 67.5% (61.7%, 69.2%) and 60.8% (53.6%, 68.2%), respectively. However, the difference of SvO2 between VM and control groups was not significant at the p = 0.05 level (p = 0.076). The SvO2 was found decreasing significantly with GA in the healthy control group (p < 0.05).ConclusionsWe report for the first time the estimation of cerebral SvO2 in human fetuses with VM using QSM. This measure of oxygen saturation might be beneficial in assessing and monitoring the metabolic status of the fetus in various clinical conditions.