Unit Volume Of Tissue Research Articles

Capillary-scale Microvessel Imaging with High-frequency Ultrasound Localization Microscopy in Mouse Brain.

Ultrasound localization microscopy is a super-resolution vascular imaging technique which has garnered substantial interest as a tool for small animal neuroimaging, neuroscience research, and the characterization of vascular pathologies. In the pursuit of increasingly high-fidelity reconstructions of microvasculature, there remains several outstanding questions concerning this sub-diffraction imaging technology, including the accurate reconstruction of microvessels approaching the capillary scale and the pragmatic challenges associated with long data acquisition times. In the context of small animal neurovascular imaging, we posit that increasing the ultrasound imaging frequency is a straightforward approach to enable higher concentrations of microbubble contrast agents, thus increasing the likelihood of microvascular/capillary mapping and decreasing the imaging duration. We demonstrate that higher frequency imaging results in improved ULM fidelity and more efficient microbubble localization due to a smaller microbubble point-spread function that is easier to localize, and which can achieve a higher localizable concentration within the same unit volume of tissue. A select example of in vivo capillary-level vascular reconstruction is demonstrated for the highest frequency imaging probe, which has substantial implications for neuroscientists investigating microvascular function in disease states, regulation, and brain development. High frequency ULM yielding a spatial resolution of 7.1μm, as measured by Fourier ring correlation, throughout the entire depth of the brain, highlighting this technology as a highly relevant tool for neuroimaging research.

Neovascularization in Outer Membrane of Chronic Subdural Hematoma : A Rationale for Middle Meningeal Artery Embolization.

Chronic subdural hematomas (cSDHs) are generally known to result from traumatic tears of bridging veins. However, the causes of repeat spontaneous cSDHs are still unclear. We investigated the changes in vasculature in the human dura mater and outer membrane (OM) of cSDHs to elucidate the cause of their spontaneous repetition. The dura mater was obtained from a normal control participant and a patient with repeat spontaneous cSDHs. The pathological samples from the patient included the dura mater and OM tightly adhered to the inner dura. The samples were analyzed with a particular focus on blood and lymphatic vessels by immunohistochemistry, 3-dimensional imaging using a transparent tissue clearing technique, and electron microscopy. The dural border cell (DBC) layer of the dura mater and OM were histologically indistinguishable. There were 5.9 times more blood vessels per unit volume of tissue in the DBC layer and OM in the patient than in the normal control. The DBC layer and OM contained pathological sinusoidal capillaries not observed in the normal tissue; these capillaries were connected to the middle meningeal arteries via penetrating arteries. In addition, marked lymphangiogenesis in the periosteal and meningeal layers was observed in the patient with cSDHs. Neovascularization in the OM seemed to originate from the DBC layer; this is a potential cause of repeat spontaneous cSDHs. Embolization of the meningeal arteries to interrupt the blood supply to pathological capillaries via penetrating arteries may be an effective treatment option.

Alteration in Microcirculation With Osteonecrosis of the Femoral Head: A Study of Dynamic Contrast-Enhanced MRI.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is commonly used in clinical practice to detect tumor blood supply, and it has recently been applied to assess skeletal vasculature. In this study, we retrospectively analyzed DCE-MRI data from 37 patients with osteonecrosis of the femoral head to evaluate alterations in microvascular circulation of the femoral head. Time-intensity curves (TICs) in the region of interest were classified into different lesion stages. In the greater trochanter area, extracellular space volume per unit volume of tissue was significantly higher in Association Research Circulation Osseous (ARCO) stage III than in ARCO stage II (P<.05 and power ≥ 0.8), while other parameters showed no statistical difference (P>.05 and/or power < 0.8). In the necrotic area, contrast enhancement ratio and maximum slope of increase were significantly lower in ARCO stage III than in ARCO stage II (P<.05 and power ≥ 0.8), while other parameters showed no statistical difference (P>.05 and/or power < 0.8). In the repair reaction area, all parameters were significantly higher in ARCO stage III than in ARCO stage II (P<.05 and power ≥ 0.8). TIC classification showed that the greater trochanter area mainly exhibited type C (plateau type), the necrotic area mainly exhibited type B (out-flow type), and the repair reaction area mainly exhibited type A (inflow type). We believe that the exchange capacity of the vessels has a much greater impact on femoral head necrosis than the number of vessels, while the generation of the repair area greatly affects the prognosis of femoral head necrosis. These findings suggest that DCE-MRI can provide a good assessment of osteonecrosis of the femoral head perfusion and can serve as a new reference for clinical treatment decisions. [Orthopedics. 2024;47(2):e73-e78.].

Quantitative dynamic contrast-enhanced parameters and intravoxel incoherent motion facilitate the prediction of TP53 status and risk stratification of early-stage endometrial carcinoma.

The aim of the study was to investigate the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion (IVIM) in differentiating TP53-mutant from wild type, low-risk from non-low-risk early-stage endometrial carcinoma (EC). A total of 74 EC patients underwent pelvic MRI. Parameters volume transfer constant (Ktrans), rate transfer constant (Kep), the volume of extravascular extracellular space per unit volume of tissue (Ve), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and microvascular volume fraction (f) were compared. The combination of parameters was investigated by logistic regression and evaluated by bootstrap (1000 samples), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). In the TP53-mutant group, Ktrans and Kep were higher and D was lower than in the TP53-wild group; Ktrans, Ve, f, and D were lower in the non-low-risk group than in the low-risk group (all P < 0.05). In the identification of TP53-mutant and TP53-wild early-stage EC, Ktrans and D were independent predictors, and the combination of them had an optimal diagnostic efficacy (AUC, 0.867; sensitivity, 92.00%; specificity, 80.95%), which was significantly better than D (Z = 2.169, P = 0.030) and Ktrans (Z = 2.572, P = 0.010). In the identification of low-risk and non-low-risk early-stage EC, Ktrans, Ve, and f were independent predictors, and the combination of them had an optimal diagnostic efficacy (AUC, 0.947; sensitivity, 83.33%; specificity, 93.18%), which was significantly better than D (Z = 3.113, P = 0.002), f (Z = 4.317, P < 0.001), Ktrans (Z = 2.713, P = 0.007), and Ve (Z = 3.175, P = 0.002). The calibration curves showed that the above two combinations of independent predictors, both have good consistency, and DCA showed that these combinations were reliable clinical prediction tools. Both DCE-MRI and IVIM facilitate the prediction of TP53 status and risk stratification in early-stage EC. Compare with each single parameter, the combination of independent predictors provided better predictive power and may serve as a superior imaging marker.

Perfusion-weighted imaging in vestibular schwannoma: the influence that cystic status and tumor size have on perfusion profiles.

The perfusion profile of vestibular schwannomas (VSs) and the factors that influence it have yet to be determined. Twenty patients with sporadic VS were analyzed by calculating parameters related to the extravascular extracellular space (EES)-the volume transfer constant between a vessel and the EES (Ktrans); the EES volume per unit of tissue volume (Ve); and the rate transfer constant between EES and blood plasma (Kep)-as well as the relative cerebral blood volume (rCBV), and by correlating those parameters with the size of the tumor and its structure (solid, cystic, or heterogeneous). Although Ktrans, Ve, and Kep were measurable in all tumors, rCBV was measurable only in large tumors. We detected a positive correlation between Ktrans and rCBV (r = 0.62, p = 0.031), a negative correlation between Ve and Kep (r = -0.51, p = 0.021), and a positive correlation between Ktrans and Ve only in solid VSs (r = 0.64, p = 0.048). Comparing the means for small and large VSs, we found that the former showed lower Ktrans (0.13 vs. 0.029, p < 0.001), higher Kep (0.68 vs. 0.46, p = 0.037), and lower Ve (0.45 vs. 0.83, p < 0.001). The mean Ktrans was lower in the cystic portions of cystic VSs than in their solid portions (0.14 vs. 0.32, p < 0.001), as was the mean Ve (0.37 vs. 0.78, p < 0.001). There were positive correlations between the solid and cystic portions for Ktrans (r = 0.71, p = 0.048) and Kep (r = 0.74, p = 0.037). In VS, tumor size appears to be consistently associated with perfusion values. In cystic VS, the cystic portions seem to have lower Ktrans and Ve than do the solid portions.

Dynamic Contrast-Enhanced MRI Parameters and Normalized ADC Values Could Aid Differentiation of Skull Base Osteomyelitis from Nasopharyngeal Cancer.

The skull base osteomyelitis sometimes can be difficult to distinguish from nasopharyngeal cancer. This study aimed to investigate the differences between skull base osteomyelitis and nasopharyngeal cancer using dynamic contrast-enhanced MR imaging and normalized ADC values. This study included 8 and 12 patients with skull base osteomyelitis and nasopharyngeal cancer, respectively, who underwent dynamic contrast-enhanced MR imaging and DWI before primary treatment. Quantitative dynamic contrast-enhanced MR imaging parameters and ADC values of the ROIs were analyzed. Normalized ADC parameters were calculated by dividing the ROIs of the lesion by that of the spinal cord. The rate transfer constant between extravascular extracellular space and blood plasma per minute (Kep) was significantly lower in patients with skull base osteomyelitis than in those with nasopharyngeal cancer (median, 0.43 versus 0.57; P = .04). The optimal cutoff value of Kep was 0.48 (area under the curve, 0.78; 95% CI, 0.55-1). The normalized mean ADC was significantly higher in patients with skull base osteomyelitis than in those with nasopharyngeal cancer (median, 1.90 versus 0.87; P < .001). The cutoff value of normalized mean ADC was 1.55 (area under the curve, 0.96; 95% CI, 0.87-1). The area under the curve of the combination of dynamic contrast-enhanced MR imaging parameters (Kep and extravascular extracellular space volume per unit tissue volume) was 0.89 (95% CI, 0.73-1), and the area under the curve of the combination of dynamic contrast-enhanced MR imaging parameters and normalized mean ADC value was 0.98 (95% CI, 0.93-1). Quantitative dynamic contrast-enhanced MR imaging parameters and normalized ADC values may be useful in differentiating skull base osteomyelitis and nasopharyngeal cancer. The combination of dynamic contrast-enhanced MR imaging parameters and normalized ADC values outperformed each measure in isolation.

Correlations of tumour permeability parameters with apparent diffusion coefficient in nasopharyngeal carcinoma.

Functional imaging has an established role in therapeutic monitoring of cancer treatments. This study evaluated the correlations of tumour permeability parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and tumour cellularity derived from apparent diffusion coefficient (ADC) in nasopharyngeal carcinoma (NPC). Twenty NPC patients were examined with DCE-MRI and RESOLVE diffusion-weighted MRI (DW-MRI). Tumour permeability parameters were quantitatively measured with Tofts compartment model. Volume transfer constant (Ktrans), volume of extravascular extracellular space (EES) per unit volume of tissue (Ve), and the flux rate constant between EES and plasma (Kep) from DCE-MRI scan were measured. The time-intensity curve was plotted from the 60 dynamic phases of DCE-MRI. The initial area under the curve for the first 60s of the contrast agent arrival (iAUC60) was also calculated. They were compared with the ADC value derived from DW-MRI with Pearson correlation analyses. Among the DCE-MRI permeability parameters, Kep had higher linearity in inverse correlation with ADC value (r=-0.69, p=<0.05). Ktrans (r=-0.60, p=<0.05) and iAUC60 (r=-0.64, p=<0.05) also had significant inverse correlations with ADC. Ve showed a significant positive correlation with ADC (r=0.63, p=<0.05). Nasopharyngeal tumour vascular permeability parameters derived from DCE-MRI scan were correlated linearly with tumour cellularity measured by free water diffusability with ADC. The clinical implementations of these linear correlations in the quantitative assessments of therapeutic response for NPC patients may be worth to further explore.

Polyploidy increases storage but decreases structural stability in Arabidopsis thaliana

Whole-genome duplication, leading to polyploidy and endopolyploidy, is widespread throughout the tree of life.1-3 Both polyploidy and endopolyploidy can increase cell size via nucleotypic effects, but the phenotypic consequences of increased cell size at the tissue and whole-organism levels are less well understood.1-4 We quantified the consequences of autopolyploidy and endopolyploidy in nine diploid accessions of Arabidopsis thaliana, representing a gradient in endopolyploidy, to their corresponding experimentally synthesized neo-tetraploid and neo-octoploid cytotypes. The increase in cell size following genome duplication increased plant storage capacity, which increased tolerance of resource limitation, but also incurred biomechanical costs because of a reduction in the amount of cell wall per unit tissue volume. Our findings also show that the functional consequences of autopolyploidy can vary with accession identity, and the presence of this variation suggests that there is potential for adaptation following whole-genome duplication.

Normalized Parameters of Dynamic Contrast-Enhanced Perfusion MRI and DWI-ADC for Differentiation between Posttreatment Changes and Recurrence in Head and Neck Cancer.

Differentiating recurrence from benign posttreatment changes has clinical importance in the imaging follow-up of head and neck cancer. This study aimed to investigate the utility of normalized dynamic contrast-enhanced MR imaging and ADC for their differentiation. This study included 51 patients with a history of head and neck cancer who underwent follow-up dynamic contrast-enhanced MR imaging with DWI-ADC, of whom 25 had recurrences and 26 had benign posttreatment changes. Quantitative and semiquantitative dynamic contrast-enhanced MR imaging parameters and ADC of the ROI and reference region were analyzed. Normalized dynamic contrast-enhanced MR imaging parameters and normalized DWI-ADC parameters were calculated by dividing the ROI by the reference region. Normalized plasma volume, volume transfer constant between extravascular extracellular space and blood plasma per minute (K trans), area under the curve, and wash-in were significantly higher in patients with recurrence than in those with benign posttreatment change (P = .003 to <.001). The normalized mean ADC was significantly lower in patients with recurrence than in those with benign posttreatment change (P < .001). The area under the receiver operating characteristic curve of the combination of normalized dynamic contrast-enhanced MR imaging parameters with significance (normalized plasma volume, normalized extravascular extracellular space volume per unit tissue volume, normalized K trans, normalized area under the curve, and normalized wash-in) and normalized mean ADC was 0.97 (95% CI, 0.93-1). Normalized dynamic contrast-enhanced MR imaging parameters, normalized mean ADC, and their combination were effective in differentiating recurrence and benign posttreatment changes in head and neck cancer.

An MRI-Based Clinical-Perfusion Model Predicts Pathological Subtypes of Prevascular Mediastinal Tumors.

This study aimed to build machine learning prediction models for predicting pathological subtypes of prevascular mediastinal tumors (PMTs). The candidate predictors were clinical variables and dynamic contrast–enhanced MRI (DCE-MRI)–derived perfusion parameters. The clinical data and preoperative DCE–MRI images of 62 PMT patients, including 17 patients with lymphoma, 31 with thymoma, and 14 with thymic carcinoma, were retrospectively analyzed. Six perfusion parameters were calculated as candidate predictors. Univariate receiver-operating-characteristic curve analysis was performed to evaluate the performance of the prediction models. A predictive model was built based on multi-class classification, which detected lymphoma, thymoma, and thymic carcinoma with sensitivity of 52.9%, 74.2%, and 92.8%, respectively. In addition, two predictive models were built based on binary classification for distinguishing Hodgkin from non-Hodgkin lymphoma and for distinguishing invasive from noninvasive thymoma, with sensitivity of 75% and 71.4%, respectively. In addition to two perfusion parameters (efflux rate constant from tissue extravascular extracellular space into the blood plasma, and extravascular extracellular space volume per unit volume of tissue), age and tumor volume were also essential parameters for predicting PMT subtypes. In conclusion, our machine learning–based predictive model, constructed with clinical data and perfusion parameters, may represent a useful tool for differential diagnosis of PMT subtypes.

Comparison of Dose and Effectiveness of a Single-Session Ultrasound-Guided High-Intensity Focused Ultrasound Ablation of Uterine Fibroids With Different Sizes.

PurposeThis study aimed to compare the dose and effectiveness of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation of uterine fibroids with different sizes and explore the effect of uterine fibroid size on dose, which provided dose evaluation for clinicians in accordance with the size of uterine fibroids.Materials and MethodsA total of 1,000 patients with symptomatic uterine fibroids who received a single-session USgHIFU treatment were enrolled in this study. The size of fibroids was divided into seven groups: 3–4 cm, 4–5 cm, 5–6 cm, 6–7 cm, 7–8 cm, 8–9 cm, and 9–11 cm. The dose was expressed on the basis of the energy efficiency factor (EEF) as the energy required for ablation per unit volume of tissue, and the non-perfused volume ratio (NPVR) was used to assess the effect of HIFU ablation.ResultsThe median NPVR of 88.3% (IQR: 80.3%–94.8%) was obtained, and no significant difference was observed among the seven groups. The classification of T2-weighted image signal intensity fibroids in the 4–5 cm group was compared with that in the 6–7 cm and 8–9 cm groups, and the difference was significant (p < 0.05). However, the proportion of T2WI hyperintense signal fibroids had no significant difference among the seven groups (p > 0.05). The median EEF was 3.88 J/mm3, and a significant difference was observed among the seven groups of EEF (p < 0.05). The EEF of groups with a fibroid size less than 6 cm was more than double the EEF of groups with a fibroid size above 6 cm. In addition, the EEF of groups with a fibroid size of 4–5 cm and 3–4 cm was 3–4 times higher than those with a fibroid size above 7 cm (p < 0.05).ConclusionsA single-session HIFU ablation for uterine fibroids of 3–11 cm can obtain an NPVR of more than 80%. The EEF decreased with the increase of the size of uterine fibroids. A fibroid size of 6.5 cm was considered as a clinical meaningful point affecting EEF.

Neurostimulation success rate of repetitive-pulse focused ultrasound in an in vivo giant axon model: An acoustic parametric study.

Focused ultrasound (FUS) is a promising tool to develop new modalities of therapeutic neurostimulation. The ability of FUS to stimulate the nervous system, in a noninvasive and spatiotemporally precise manner, has been demonstrated in animals and human subjects, but the underlying biomechanisms are not fully understood yet. The objective of the present study was to investigate the bioeffects involved in the generation of trains of action potentials (APs) by repetitive-pulse FUS stimuli in a simple invertebrate neural model. The respective influences of different acoustic parameters on the neurostimulation success rate (NSR), defined as the rate of FUS stimuli capable of evoking at least one AP, were explored using the system of afferent nerves and giant fibers of Lumbricus terrestris as neural model. Each parameter was studied independently by administering random FUS sequences while keeping all but one FUS parameter constant. The NSR was evaluated as a function of (i) the spatial-average pulse-average intensity (Isapa ); (ii) the pulse duration (PD); (iii) the pulse repetition frequency (PRF); iv) the number of cycles per pulse (Ncycles ); (v) two ultrasound frequencies, f0 =1.1MHz and f3 =3.3MHz, corresponding to the fundamental and third-harmonic resonant frequencies of the FUS transducer, respectively (spherical, radius of curvature: 50mm); and (vi) levels of emerging stable cavitation and inertial cavitation. The NSR associated to 1.1MHz repetitive-pulse FUS stimuli was found to increase as a function of increasing Isapa , PD, PRF, and Ncycles . When evaluating each parameter at f=1.1MHz, it was observed that NSRs close to 100% were achieved when sufficiently elevating their respective values. When computing the NSR as a function of the spatial-average, temporal-average intensity (Isata ), defined as the product of PRF, PD, and Isapa , a significant elevation of the NSR from 0% to close to 100% was measured by increasing Isata from values approximate to 4 W/cm2 to values higher than 12 W/cm2 . No clear and consistent trend was observed in trials aimed at exploring the effects of different levels of stable and inertial acoustic cavitation on the NSR. Finally, the feasibility of inducing neural responses with 3.3MHz repetitive-pulse FUS stimuli was also demonstrated with NSRs reaching up to 60%, in the range of FUS parameters studied. The time-averaged value of the radiation force per unit volume of tissue is proportional to the acoustic intensity. As a result, the observations from this study suggest that the neural structure responding to the stimulus is sensitive to the mean radiation force carried by the FUS sequence, regardless of the combination of FUS parameters giving rise to such force. The results from this study further revealed the existence of a minimal activation threshold with regard to Isapa .

Quantitative perfusion histogram parameters of dynamic contrast-enhanced MRI to identify different pathological types of uterine leiomyoma.

:To explore the value of quantitative perfusion histogram parameters of dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI） in pathological classification of uterine leiomyoma and its correlation with Ki-67 protein expression. Thirty five patients with uterine leiomyoma confirmed by operation and pathology at Shaoxing People's Hospital from October 2015 to September 2017 were analyzed retrospectively，including 15 cases of ordinary type，8 cases of cellular type and 12 cases of degenerative type. All patients were examined by pelvic DCE-MRI before operation，and the histogram parameters （median，mean，skewness，kurtosis，energy，entropy） of various quantitative perfusion parameters，including volume transport constant （K），rate constant （K），extravascular extracellular space distribute volume per unit tissue volume （V），blood plasma volume per unit volume of tissue （V） were calculated，and the efficacy of different parameters in pathological classification of uterine leiomyoma was evaluated by ROC curve. The expression of Ki-67 protein in uterine leiomyoma was detected by immunohistochemical method，and the correlation between histogram parameters and Ki-67 protein expression was analyzed by Pearson and Spearman correlation analysis. The median and mean values of K，K，V and V in the cellular group were higher than those in the degenerative group and the ordinary group（<0.05 or <0.01），while the skewness of V，the skewness and kurtosis of K in the cellular group were lower than those in the ordinary group （all <0.05）. The entropy of K in the cellular group was higher than that in the degenerative group and the ordinary group （all < 0.05）. The entropy of V in the cellular group was higher than that in the ordinary group （<0.01）. The median，mean，skewness of K，median and mean of K，median and mean of V，median，mean，energy and entropy of V were correlated with Ki-67 expression（all <0.05）. The results of ROC curve analysis showed that the median threshold of K was 0.994/min，the sensitivity and specificity for the diagnosis of cellular uterine leiomyoma were 100.0% and 77.8% respectively，and the area under the ROC curve was 0.949. When the mean threshold of K was 1.170/min，the sensitivity and specificity for diagnosing cellular uterine leiomyoma were 100.0% and 77.8% respectively，and the area under the ROC curve was 0.958. The area under the ROC curve of K （entropy），K （median，mean），V （median，mean，entropy） in the diagnosis of cellular uterine leiomyoma were 0.755-0.907. :DCE-MRI quantitative perfusion histogram parameters have high diagnostic value in differentiating pathological types of uterine leiomyoma，especially for cellular uterine leiomyoma.

Multiparameter MRI and Clinical Factors for Predicting Early Response to Chemoradiotherapy in Cervical Cancer.

HomeRadiology: Imaging CancerVol. 3, No. 1 PreviousNext Research HighlightsFree AccessMultiparameter MRI and Clinical Factors for Predicting Early Response to Chemoradiotherapy in Cervical CancerSanaz Javadi, Vikas KundraSanaz Javadi, Vikas KundraSanaz JavadiVikas KundraPublished Online:Jan 29 2021https://doi.org/10.1148/rycan.2021209038MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked InEmail Take-Away Points■ Major Focus: To assess a combination of multiparametric MRI with clinical prognostic factors for predicting treatment outcomes in patients with cervical cancer.■ Key Result: Pretreatment individual multiple MRI parameters (diffusion coefficient, volume transfer constant, and extravascular extracellular space) and stage were found to be independent prognostic factors for prediction. Combining multiple MRI parameters, multiparametric MRI biomarkers, and their combination with clinical stage can parse categories favorable, intermediate, and unfavorable for recurrence after chemoradiotherapy.■ Impact: Further assessment of this combination is warranted for improving prediction of treatment responses in patients with cervical cancer.Cervical cancer is the fourth most common cause of cancer-related mortality in women globally. Chemoradiotherapy is the treatment of choice for locally advanced cervical cancer. Early prediction of treatment response could provide a window of opportunity to modify therapy if needed. Clinical prognostic factors alone have limitations in prediction of early response. A few studies have shown functional imaging methods, including PET and diffusion-weighted MRI, can predict recurrence and response to treatment in patients with cervical cancer (1–3). Zheng et al studied this topic further by combining pre- and posttreatment MRI parameters (intravoxel incoherent motion [IVIM], dynamic contrast-enhanced [DCE] MRI, and apparent diffusion coefficient [ADC]) with clinical prognostic factors (squamous cell carcinoma antigen, tumor stage, histologic type, and lymphadenopathy) to predict response to chemoradiotherapy in patients with cervical cancer.The study included 85 patients with pathologically proven cervical cancer that was greater than 1 cm who had no prior history of chemotherapy or radiation therapy and underwent pre- and posttreatment MRI. The latter was used to assess recurrence using Response Evaluation Criteria in Solid Tumors. Treatment included a combination of external beam radiotherapy, high-dose-rate intracavitary brachytherapy, and concurrent cisplatin chemotherapy. One month after completion of chemoradiotherapy, 40% of patients had residual disease. Patients with residual disease had higher stage but no other differences in clinical prognostic factors.Higher pretreatment ADC, IVIM diffusion-related coefficient (D), and DCE volume of extravascular extracellular space per unit volume of tissue (Ve), as well as lower IVIM perfusion-related parameter (f) and DCE volume transfer constant from blood plasma to the extravascular extracellular space (Ktrans) values were seen in tumors with residual disease on univariate analysis. The authors suggest that higher pretreatment ADC and D values may identify tumor necrosis, whereas high Ve, lower f value, and lower Ktrans may reflect poorer blood supply with decreased drug delivery and hypoxia causing resistance to radiation therapy.Multivariate analysis showed sensitivity and specificity of MRI parameters for predicting posttreatment residual tumor as 82% and 65% for D, 67% and 90% for Ktrans, and 82% and 71% for Ve, respectively. Combining these MRI parameters, the sensitivity and specificity for predicting residual disease were 91% and 90%, respectively. MRI parameters and International Federation of Gynecology and Obstetrics (FIGO) stage together produced 85% sensitivity and 96% specificity. MRI parameters with and without FIGO stage segregated patients into favorable, intermediate, and unfavorable categories for residual tumor recurrence. The study suggests that the combination of multiparametric MRI and clinical stage can predict response to treatment in cervical cancer.Highlighted ArticleZheng X, Guo W, Dong J, Qian L. Prediction of early response to concurrent chemoradiotherapy in cervical cancer: Value of multi-parameter MRI combined with clinical prognostic factors. Magn Reson Imaging 2020;72:159–166. doi: https://doi.org/10.1016/j.mri.2020.06.014

Non-Invasive Estimation of Glioma IDH1 Mutation and VEGF Expression by Histogram Analysis of Dynamic Contrast-Enhanced MRI.

ObjectivesTo investigate whether glioma isocitrate dehydrogenase (IDH) 1 mutation and vascular endothelial growth factor (VEGF) expression can be estimated by histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).MethodsChinese Glioma Genome Atlas (CGGA) database was wined for differential expression of VEGF in gliomas with different IDH genotypes. The VEGF expression and IDH1 genotypes of 56 glioma samples in our hospital were assessed by immunohistochemistry. Preoperative DCE-MRI data of glioma samples were reviewed. Regions of interest (ROIs) covering tumor parenchyma were delineated. Histogram parameters of volume transfer constant (Ktrans) and volume of extravascular extracellular space per unit volume of tissue (Ve) derived from DCE-MRI were obtained. Histogram parameters of Ktrans, Ve and VEGF expression of IDH1 mutant type (IDH1mut) gliomas were compared with the IDH1 wildtype (IDH1wt) gliomas. Receiver operating characteristic (ROC) curve analysis was performed to differentiate IDH1mut from IDH1wt gliomas. The correlation coefficients were determined between histogram parameters of Ktrans, Ve and VEGF expression in gliomas.ResultsIn CGGA database, VEGF expression in IDHmut gliomas was lower as compared to wildtype counterpart. The immunohistochemistry of glioma samples in our hospital also confirmed the results. Comparisons demonstrated statistically significant differences in histogram parameters of Ktransand Ve [mean, standard deviation (SD), 50th, 75th, 90th. and 95th percentile] between IDH1mutand IDH1wtgliomas (P < 0.05, respectively). ROC curve analysis revealed that 50th percentile of Ktrans (0.019 min−1) and Ve (0.039) provided the perfect combination of sensitivity and specificity in differentiating gliomas with IDH1mutfrom IDH1wt. Irrespective of IDH1 mutation, histogram parameters of Ktransand Ve were correlated with VEGF expression in gliomas (P < 0.05, respectively).Conclusions VEGF expression is significantly lower in IDH1mut gliomas as compared to the wildtype counterpart, and it is non-invasively predictable with histogram analysis of DCE-MRI.

Prognostic value of CT perfusion and permeability imaging in traumatic brain injury.

Currently established prognostic models in traumatic brain injury (TBI) include noncontrast computed tomography (CT) which is insensitive to early perfusion alterations associated with secondary brain injury. Perfusion CT (PCT) on the other hand offers insight into early perfusion abnormalities. We hypothesized that adding CT perfusion and permeability data to the established outcome predictors improves the performance of the prognostic model. A prospective cohort study of consecutive 50 adult patients with head injury and Glasgow Coma Scale score of 12 or less was performed at a single Level 1 Trauma Centre. Perfusion CT was added to routine control CT 12 hours to 24 hours after admission. Region of interest analysis was performed in six major vascular territories on perfusion and permeability parametric maps. Glasgow Outcome Scale (GOS) was used 6 months later to categorize patients' functional outcomes to favorable (GOS score > 3) or unfavorable (GOS score ≤ 3). We defined core prognostic model, consisting of age, motor Glasgow Coma Scale score, pupillary reactivity, and CT Rotterdam Score. Next, we added perfusion and permeability data as predictors and compared updated models to the core model using cross-validated areas under the receiver operator curves (cv-AUC). Significant advantage over core model was shown by the model, containing both mean cerebral extravascular-extracellular volume per unit of tissue volume and cerebral blood volume of the least perfused arterial territory in addition to core predictors (cv-AUC, 0.75; 95% confidence interval, 0.51-0.84 vs. 0.6; 95% confidence interval, 0.37-0.74). The development of cerebral ischemia and traumatic cerebral edema constitutes the secondary brain injury and represents the target for therapeutic interventions. Our results suggest that adding CT perfusion and permeability data to the established outcome predictors improves the performance of the prognostic model in the setting of moderate and severe TBI. Prognostic study, level III.

Volume-based histogram analysis of dynamic contrast-enhanced MRI for estimation of gliomas IDH1 mutation status

PurposeThe study aimed to investigate whether isocitrate dehydrogenase 1 (IDH1) mutation status in gliomas can be estimated by volume-based histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Materials and methodsPreoperative DCE-MRI data of 85 pathologically confirmed glioma patients including 33 carrying IDH1 mutant type (IDH1mut) and 52 with IDH1 wildtype (IDH1wt) were reviewed in a retrospective approach. Regions of interest (ROI) covering entire tumor volume were manually delineated using O.K. software (OmniKinetics, GE Healthcare, China). Histogram parameters of volume transfer constant (Ktrans) and volume of extravascular /extracellular space per unit volume of tissue (Ve) derived from DCE-MRI were obtained. Mann-Whitney U tests were made to compare the differences in histogram parameters of Ktrans and Ve between IDH1mut and IDH1wt in all gliomas and high-grade gliomas (HGGs, grade III and IV). Receiver operator characteristic (ROC) analysis were implemented to assess the diagnostic performance. ResultsIn histogram parameters of Ktrans and Ve, pairwise comparisons demonstrated statistically significant differences in mean, standard deviation (SD), 90th and 95th percentiles (90%, 95%) values between IDH1mut and IDH1wt in all cases of gliomas and HGGs (P < 0.05, respectively). The ROC analysis revealed that the cut-off values of 95% value of Ktrans (0.097 min-1) and mean value of Ve (0.099) provided the best combination of sensitivity and specificity to distinguish all gliomas with IDH1mut from IDH1wt. In HGGs, the cut-off values of mean value of Ktrans and Ve (0.044 min-1, 0.099) played similar role. ConclusionVolume-based histogram analysis of DCE-MRI performs well in identification of IDH1mut gliomas.

Synthesis of L-Dihydroxyphenylalanine by Monoenzymatic Tyrosine Hydroxylase-Containing Nerve Fibers in the Suprachiasmatic Nucleus in Rats during Ontogeny

Abstract—The suprachiasmatic nucleus (SCN) regulates the functioning of the body in accordance with circadian rhythms thanks to the pacemaker neurons present in it and afferents modulating these neurons. One of the afferents is represented by nerve fibers containing only the first enzyme for the synthesis of catecholamines, tyrosine hydroxylase (TH). In ontogeny, the concentration of these fibers (amount per unit volume of tissue) reaches a maximum on the 10th postnatal day (P10), and then gradually decreases. The aim of this work was to verify our assumption that, in TH-containing fibers in SCN of rats, L-DOPA is synthesized from L-tyrosine as the final secretory product, and the efficiency of this synthesis is higher in the early postnatal period than in adults. The synthesis of L-DOPA was evaluated by an increase in the total content of L-DOPA in SCN and in the incubation medium after a two-hour incubation of SCN in a medium with or without L‑tyrosine. We found that the addition of L-tyrosine to the incubation medium led to a multifold increase in the total L-DOPA content in SCN and in the medium, which is evidence of the synthesis of L-DOPA as a final product in TH-containing fibers. A comparative analysis of the synthesis of L-DOPA in SCN at P10 and P60 showed that the synthesis rate (a ratio between the total content of L-DOPA in SCN and in the incubation medium to the incubation time) at P60 exceeds the synthesis rate at P10, while the efficiency of L‑DOPA synthesis (a ratio between the rate of L-DOPA synthesis and the total protein content in SCN) is higher at P10. Thus, we obtained evidence of L-DOPA synthesis in TH-containing SCN nerve fibers, and the efficiency of this synthesis in rats in the early postnatal period is higher than in adult animals.

Polyunsaturated Fatty Acid Content in Muscle Tissue Is Associated with the Duration of Embryo Development in Salmonoid Fishes (Salmonoidei).

A hypothesis was advanced and grounded that the total content of eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic (DHA, 22:6n-3) acids in fish muscle tissue is associated with the species-specific (taxon-specific) duration of embryo development. A meta-analysis of the original and published data was performed using fishes of the families Coregonidae and Salmonidae as an example. Fishes with longer embryo development times, which are observed at lower temperatures, were found to have significantly higher EPA + DHA contents in muscles as compared with the species that belong to the same families but have shorter embryo development times. This association was explained by the fact that an embryo forms more cells per unit tissue volume at lower temperatures, which requires a greater specific amount of cell membranes and, therefore, greater amounts of EPA and DHA to produce them.

Benign or Malignant Characterization of Soft-Tissue Tumors by Using Semiquantitative and Quantitative Parameters of Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

To evaluate the efficacy of the semiquantitative and quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in differentiating between benign and malignant soft-tissue tumors. A total of 45 patients with pathologically confirmed soft-tissue tumors (15 benign and 30 malignant tumors) underwent DCE-MRI. The semiquantitative parameters assessed were as follows: time to peak (TTP), maximum concentration (MAX Conc), area under the curve of time-concentration curve (AUC-TC), and maximum rise slope (MAX Slope). Quantitative DCE-MRI was analyzed with the extended Tofts-Kety model to assess the following quantitative parameters: volume transfer constant (Ktrans), microvascular permeability reflux constant (Kep), and distribute volume per unit tissue volume (Ve). Data were evaluated using the independent t test or Mann-Whitney U test and receiver operating characteristic (ROC) curves. The TTP (P = .0035), MAX Conc (P = .0018), AUC-TC (P = .0018), MAX Slope (P = .0018), Ktrans (P = .0018), and Kep (P = .0035) were significantly different between the benign and malignant soft-tissue tumors. The AUC of the ROC curve demonstrated the diagnostic potential of TTP (0.778), MAX Conc (0.849), AUC-TC (0.831), MAX Slope (0.847), Ktrans (0.836), Kep (0.778), and Ve (0.638). The use of semiquantitative and quantitative parameters of DCE-MRI enabled differentiation between benign and malignant soft-tissue tumors. The values of TTP were lower, while those of MAX Conc, AUC-TC, MAX Slope, Ktrans, and Kep were higher in malignant than in benign tumors.