Unit Volume Of Tissue Research Articles

A Novel Transducer for Measurement of Skin Blood Flow Using Radio Frequency Energy

Abstract The rate of blood flow in the skin has relevance to several cardiovascular conditions of clinical significance. However, there is no accepted fast, easy way to noninvasively measure the volumetric rate of blood flow per unit tissue volume. Previous work has suggested the potential for using skin heating from radio frequency (RF) energy in the millimeter wave (MMW) band, with simultaneous monitoring of skin surface temperature as a means for noninvasive skin blood flow measurement. This work presents a design and in vitro test results for a simple transducer for MMW blood flow measurement. The transducer consists of a Ka band microstrip antenna and an infrared temperature sensor integrated in a thermoplastic housing. A prototype was tested in a controlled flow chamber, using a commercial tissue phantom material. The device was tested at eight flow rates ranging from 0.25 ml min−1 to 20 ml min−1, equivalent to approximately 10–800 ml min−1·per 100 cm3 of tissue. The differences in temperature increase at exposure time t=60 s were statistically significant (n = 5) so as to allow resolution of flow rates of 0.25, 0.50, 1.0, 2.0, 10, and 20 ml min−1. The ensemble average of temperature increase versus time over the 60 s exposure window were described by a simple two-parameter lumped model which can be correlated with the flow rate. The flow rate model parameter does not scale directly with the flow in the experimental chamber however. This may suggest limitations either in the model or the experimental procedure.

Quantitative Assessment of Tumor Cell Proliferation in Brain Gliomas with Dynamic Contrast-Enhanced MRI

This study aimed to investigate whether volume transfer constant (Ktrans) and volume of extravascular extracellular space per unit volume of tissue (Ve) derived from dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) could quantitatively assess the tumor proliferation index (Ki-67) of gliomas noninvasively. The preoperative DCE MRI data of 69 patients with pathologically confirmed glioma (28, 8, and 33 cases in grades Ⅱ, Ⅲ, and Ⅳ) were retrospectively reviewed. The maximal Ktrans and Ve were measured in the tumor body. The immunohistochemistry was used to detect the expression of Ki-67 proteins in glioma specimens. The Mann-Whitney U test was applied to analyze the differences in Ktrans, Ve, and Ki-67 index across histologically defined glioma grades. Spearman correlation was performed between Ktrans, Ve, and Ki-67 index. The receiver operating characteristic curve analysis was used to determine the cutoff values of Ktrans and Ve in distinguishing different Ki-67 index expression levels. Ktrans, Ve, and Ki-67 index of grade Ⅱ (0.027 min-1, 0.065, 4.04%) were significantly lower than those of grade Ⅲ (0.093 min-1, 0.297, 25.13%) and Ⅳ (0.100 min-1, 0.299, 25.37%). Both Ktrans and Ve significantly correlated with the Ki-67 index in all tumors and high-grade gliomas (HGGs, grade Ⅲ and Ⅳ). The receiver operating characteristic curve analysis revealed that the cutoff values for Ktrans (0.079 min-1) and Ve (0.249) provided the best combination of sensitivity and specificity to distinguish the gliomas with high Ki-67 index from those with low Ki-67 index. The DCE MRI-derived parameters were valuable in assessing the tumor cell proliferation in HGG noninvasively.

Blood-Brain Barrier Permeability in Aneurysmal Subarachnoid Hemorrhage: Correlation With Clinical Outcomes.

The current understanding of the utility of blood-brain barrier permeability (BBBP) evaluation with extended-pass perfusion CT in the clinical setting is limited. We assessed whether BBBP parameters evaluated with perfusion CT correlate with unfavorable clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). A retrospective cross-sectional analysis was performed of 22 patients who underwent perfusion CT on days 0-3 after SAH. Extended perfusion CT data were postprocessed into BBBP quantitative maps of kep (washout rate constant of contrast agent from the extravascular extracellular space [EES] to the intravascular space), PS (permeability surface area product), Ktrans (volume transfer constant from blood plasma to EES), and Ve (EES volume per unit tissue volume) using Olea Sphere software (version 2.0). Clinical outcomes data regarding the presence of permanent neurologic deficits and modified Rankin scores were collected at discharge. ROC curve analyses and unpaired t tests were performed. The 22 patients were stratified on the basis of their clinical outcomes of permanent neurologic deficit and modified Rankin scores. In patients with unfavorable clinical outcomes (i.e., patients with permanent neurologic deficit and those with modified Rankin scores of 3-6), PS and Ve were significantly increased and kep and Ktrans were significantly decreased. A multiparameter ROC curve analysis combining the four parameters yielded an AUC of 0.80 for permanent neurologic deficit and an AUC of 0.89 for modified Rankin scores of 3-6. SAH patients with unfavorable outcomes had significantly elevated PS and Ve and significantly decreased kep, indicating increased BBBP, compared with SAH patients with unfavorable outcomes. Evaluation of BBBP parameters may provide prognostication of unfavorable outcomes in patients with SAH and help guide management.

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone.

Pirfenidone is a novel anti-fibrotic agent in idiopathic pulmonary fibrosis with proven clinical benefit. Better human tissue models to demonstrate the immunomodulatory and anti-fibrotic effect of pirfenidone are required. The purpose of the study was to use transbronchial lung cryobiopsy (TBLC), a novel technique which provides substantial tissue samples, and a large panel of biomarkers to temporally assess disease activity and response to pirfenidone therapy. Thirteen patients with confirmed idiopathic pulmonary fibrosis (IPF) underwent full physiological and radiological assessment at diagnosis and after 6-month pirfenidone therapy. They underwent assessment for a wide range of potential serum and bronchoalveolar lavage biomarkers of disease activity. Finally, they underwent TBLC before and after treatment. Tissue samples were assessed for numbers of fibroblast foci, for Ki-67, a marker of tissue proliferation and caspase-3, a marker of tissue apoptosis. All patients completed treatment and investigations without significant incident. There was no significant fall in number of fibroblast foci per unit tissue volume after treatment (pre-treatment: 0.14/mm2 vs. post-treatment 0.08/mm2, p = 0.1). Likewise, there was no significant change in other markers of tissue proliferation, Ki-67 or Caspase-3 with pirfenidone treatment. We found an increase in three bronchoalveolar lavage angiogenesis cytokines, Placental Growth Factor, Vascular Endothelial Growth Factor-A, and basic Fibroblast Growth Factor, two anti-inflammatory cytokines Interleukin-10 and Interleukin-4 and Surfactant Protein-D. TBLC offers a unique opportunity to potentially assess the course of disease activity and response to novel anti-fibrotic activity in IPF.

Diagnostic value of diffusion kurtosis imaging combined with quantitative dynamic contrast-enhanced MRI in breast lesions

Objective To evaluate the diagnostic efficacy of MRI diffusion kurtosis imaging (DKI) and quantitative dynamic contrast enhancement MRI (DCE-MRI) in benign and malignant breast lesions, and to explore the differential diagnosis ability for different pathological types and molecular subtype lesions. Methods Sixty four females were retrospectively enrolled in the study of MRI diffusion kurtosis imaging and quantitative dynamic contrast enhancement between November 20 and May 2017. All of them were confirmed to have benign or malignant lesions after surgical resection or puncture. All patients underwent axial T1WI, DKI and DCE-MRI examinations. The mean kurtosis (MK) and mean diffusivity (MD) values were calculated by the DKI model, and the hemodynamic parameters were obtained by quantitative dynamic contrast enhancement, including volume transfer constant (Ktrans), rate constant (Kep), extravascular extracellular space distribute volume per unit tissue volume (Ve) and blood volume fraction (Vp). Pathological analysis was performed to monitor the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) and nuclear proliferation index Ki67. The breast cancer was divided into Luminal A type, Luminal B type, HER-2 positive and triple-negative 4 subtypes. The differences of DKI parameters and DCE-MRI parameters between benign and malignant breast lesions were compared using two independent samples t test (normal distribution and homogeneity of variance) or Mann-Whitney U test (skewed distribution or variance). ROC analysis was used to evaluate the value of DKI and DCE-MRI parameters in differential diagnosis of benign and malignant breast lesions with pathological results as the gold standard. The Mann-Whitney U test and Kruskal-Wallis H test were used to compare the differences of DKI and DCE-MRI parameters among different prognostic factors and molecular subtypes of breast cancer. Spearman rank correlation analysis was used to evaluate the correlation between DKI and DCE-MRI parameters and different prognostic factors. Results Sixty-four cases were single lesions, with breast cancer in 23 cases and 41 cases of benign lesions. In breast cancer, there were 9 cases of Luminal A type, 7 cases of Luminal B type, 3 cases of HER-2 positive type and 4 cases of triple negative type. The positive numbers of ER, PR and HER-2 were 14, 11 and 10 cases respectively. Nineteen cases showed high expression of Ki67, while 4 cases showed low expression. There were significant differences in MK, MD, Ktrans and Kep between benign and malignant lesions (P 0.05).The area under the ROC for the differential diagnosis of benign and malignant breast lesions were 0.897, 0.808, 0.844 and 0.842, respectively. The combined multi-parameter differential diagnosis improved the efficacy. Combined with the above four parameters, the area under the ROC was 0.950. The diagnosis Sensitivity, specificity and accuracy were 0.870, 0.951 and 0.922 respectively. The Ktrans and Vp values of patients with ER positive and ER negative, as well as Ve value of deferent lymph node status, were significantly different (P 0.05). There was a moderate positive correlation between ER and Ktrans and Vp values. There was a low positive correlation between lymph node status and Ve value (r= 0.6, 0.5 and 0.4, respectively, P 0.05). There were no significant differences in DKI and DCE-MRI parameters among different subtypes of breast cancer patients (all P>0.05). Conclusion DKI combined with DCE-MRI can improve the differential diagnosis of breast lesions and some DCE-MRI parameters are related to prognostic factors. Key words: Breast neoplasms; Magnetic resonance imaging; Diffusion kurtosis imaging; Quantitative dynamic contrast enhancement

Contrast-enhanced dynamic and diffusion-weighted magnetic resonance imaging at 3.0 T to assess early-stage nasopharyngeal carcinoma.

The present study aimed to assess early-stage nasopharyngeal carcinoma (NPC) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) at 3.0 T. A total of 44 patients newly diagnosed with NPC were included in the present study. All patients underwent MR examination at 3.0 T using DCE-MRI and DWI. The volume transfer constant (Ktrans ), flux rate constant between extravascular extracellular space and plasma (Kep ), the volume of extravascular extracellular space per unit volume of tissue (Ve ) and the apparent diffusion coefficient (ADC) of tumours were investigated. Furthermore, the correlation between clinical stages and ADC value and Ktrans were analysed. The diagnostic accuracy of Ktrans and ADC were estimated using receiver operating characteristic curves. NPC stage correlated positively with Ktrans and negatively with ADC values. Additionally, tumour Ktrans negatively correlated with ADC value. The sensitivity and accuracy of combined Ktrans and ADC in distinguishing between stage II and stage III and stage III and IV were higher than the values of either measurement used separately. The present study suggested that Ktrans and ADC derived from DCE-MRI and DWI may be useful to detect stage early NPC accurately. Ktrans and ADC in combination were superior than either alone.

Measurement of the permeability, perfusion, and histogram characteristics in relapsing-remitting multiple sclerosis using dynamic contrast-enhanced MRI with extended Tofts linear model.

To investigate the application value of using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with extended Tofts linear model for relapsing-remitting multiple sclerosis (RRMS) and its correlation with expanded disability status scale (EDSS) scores and disease duration. Thirty patients with multiple sclerosis (MS) underwent conventional magnetic resonance imaging (MRI) and DCE-MRI with a 3.0 Tesla MR scanner. An extended Tofts linear model was used to quantitatively measure MR imaging biomarkers. The histogram parameters and correlation among imaging biomarkers, EDSS scores, and disease duration were also analyzed. The MR imaging biomarkers volume transfer constant (Ktrans), volume of the extravascular extracellular space per unit volume of tissue (Ve), fractional plasma volume (Vp), cerebral blood flow (CBF), and cerebral blood volume (CBV) of contrast-enhancing (CE) lesions were significantly higher (P < 0.05) than those of nonenhancing (NE) lesions and normal-appearing white matter (NAWM) regions. The skewness of Ve value in CE lesions was more close to normal distribution. There was no significant correlation among the biomarkers with the EDSS scores and disease duration (P > 0.05). Our study demonstrates that the DCE-MRI with the extended Tofts linear model can measure the permeability and perfusion characteristic in MS lesions and in NAWM regions. The Ktrans, Ve, Vp, CBF, and CBV of CE lesions were significantly higher than that of NE lesions. The skewness of Ve value in CE lesions was more close to normal distribution, indicating that the histogram can be helpful to distinguish the pathology of MS lesions.

Application of whole-lesion histogram analysis of pharmacokinetic parameters in dynamic contrast-enhanced MRI of breast lesions with the CAIPIRINHA-Dixon-TWIST-VIBE technique.

To investigate the application of whole-lesion histogram analysis of pharmacokinetic parameters for differentiating malignant from benign breast lesions on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). In all, 92 women with 97 breast lesions (26 benign and 71 malignant lesions) were enrolled in this study. Patients underwent dynamic breast MRI at 3T using a prototypical CAIPIRINHA-Dixon-TWIST-VIBE (CDT-VIBE) sequence and a subsequent surgery or biopsy. Inflow rate of the agent between plasma and interstitium (Ktrans ), outflow rate of agent between interstitium and plasma (Kep ), extravascular space volume per unit volume of tissue (ve ) including mean value, 25th/50th/75th/90th percentiles, skewness, and kurtosis were then calculated based on the whole lesion. A single-sample Kolmogorov-Smirnov test, paired t-test, and receiver operating characteristic curve (ROC) analysis were used for statistical analysis. Malignant breast lesions had significantly higher Ktrans , Kep , and lower ve in mean values, 25th/50th/75th/90th percentiles, and significantly higher skewness of ve than benign breast lesions (all P < 0.05). There was no significant difference in kurtosis values between malignant and benign breast lesions (all P > 0.05). The 90th percentile of Ktrans , the 90th percentile of Kep , and the 50th percentile of ve showed the greatest areas under the ROC curve (AUC) for each pharmacokinetic parameter derived from DCE-MRI. The 90th percentile of Kep achieved the highest AUC value (0.927) among all histogram-derived values. The whole-lesion histogram analysis of pharmacokinetic parameters can improve the diagnostic accuracy of breast DCE-MRI with the CDT-VIBE technique. The 90th percentile of Kep may be the best indicator in differentiation between malignant and benign breast lesions. 4 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2018;47:91-96.

Sublingual microcirculatory blood flow and vessel density in Sherpas at high altitude.

Anecdotal reports suggest that Sherpa highlanders demonstrate extraordinary tolerance to hypoxia at high altitude, despite exhibiting lower arterial oxygen content than acclimatized lowlanders. This study tested the hypothesis that Sherpas exposed to hypobaric hypoxia on ascent to 5,300 m develop increased microcirculatory blood flow as a means of maintaining tissue oxygen delivery. Incident dark-field imaging was used to obtain images of the sublingual microcirculation from 64 Sherpas and 69 lowlanders. Serial measurements were obtained from participants undertaking an ascent from baseline testing (35 m or 1,300 m) to Everest base camp (5,300 m) and following subsequent descent in Kathmandu (1,300 m). Microcirculatory flow index and heterogeneity index were used to provide indexes of microcirculatory flow, while capillary density was assessed using small vessel density. Sherpas demonstrated significantly greater microcirculatory blood flow at Everest base camp, but not at baseline testing or on return in Kathmandu, than lowlanders. Additionally, blood flow exhibited greater homogeneity at 5,300 and 1,300 m (descent) in Sherpas than lowlanders. Sublingual small vessel density was not different between the two cohorts at baseline testing or at 1,300 m; however, at 5,300 m, capillary density was up to 30% greater in Sherpas. These data suggest that Sherpas can maintain a significantly greater microcirculatory flow per unit time and flow per unit volume of tissue at high altitude than lowlanders. These findings support the notion that peripheral vascular factors at the microcirculatory level may be important in the process of adaptation to hypoxia.NEW & NOTEWORTHY Sherpa highlanders demonstrate extraordinary tolerance to hypoxia at high altitude, yet the physiological mechanisms underlying this tolerance remain unknown. In our prospective study, conducted on healthy volunteers ascending to Everest base camp (5,300 m), we demonstrated that Sherpas have a higher sublingual microcirculatory blood flow and greater capillary density at high altitude than lowlanders. These findings support the notion that the peripheral microcirculation plays a key role in the process of long-term adaptation to hypoxia.

Perfusion Parameters on Breast Dynamic Contrast-Enhanced MRI Are Associated With Disease-Specific Survival in Patients With Triple-Negative Breast Cancer.

The aim of this study was to investigate the association between perfusion parameters on MRI performed before treatment and survival outcome (disease-free survival [DFS], disease-specific survival [DSS]) in patients with triple-negative breast cancer (TNBC). Sixty-one patients (median age, 50 years; age range, 27-77 years) with TNBC (tumor size on MRI: median, 25.5 mm; range, 11.0-142.0 mm) were included. We analyzed clinical and pathologic variables and MRI parameters. Cox proportional hazards models were used to determine associations with survival outcome. The median follow-up time was 46.1 months (range, 13.9-58.4 months). Eleven of 61 (18.0%) patients had events (i.e., local, regional, or distant recurrence or contralateral breast cancer) and seven (11.5%) died of breast cancer. Among the pretreatment variables, a larger tumor size on MR images (hazard ratio [HR] = 1.024, p = 0.003) was associated with worse DFS at univariate analysis. In multivariate pretreatment models for DSS, a higher fractional volume of extravascular extracellular space per unit volume of tissue (ve) value (HR = 1.658, p = 0.038), higher peak enhancement (HR = 1.843, p = 0.018), and a larger tumor size on MR images (HR = 1.060, p = 0.001) were associated with worse DSS. In multivariate posttreatment models, a larger pathologic tumor size (HR for DFS, 1.074 [p = 0.005]; HR for DSS, 1.050 [p = 0.042]) and metastasis in surgically resected axillary lymph nodes (HR for DFS, 5.789 [p = 0.017]; HR for DSS, 23.717 [p = 0.005]) were associated with worse survival outcome. A higher ve value, higher peak enhancement, and larger tumor size of the primary tumor on pretreatment MRI were independent predictors of worse DSS in patients with TNBC.

Correlation of quantitative parameters on dynamic contrast-enhanced MRI with prognostic factors of breast carcinoma

Objective To investigate the correlation between parameters obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and prognostic factors (including enhanced morphology, tumor size, histological grade, nuclear grade) of breast carcinoma. Methods One hundred and thirteen breast cancer cases with 120 lesions confirmed histopathologically were retrospectively analyzed. All the patients underwent the DCE-MRI before the surgery, and the immunohistochemistry after the operation was performed to get the histological and nuclear grade. The volume transfer constant(Ktrans), rate constant (kep), and volume of extravascular extracellular space per unit volume of tissue(ve) were calculated through the DCE-MRI postprocessing. One hundred and three invasive ductal carcinomas were examined with the immunohistochemistry to get results of the histological and nuclear grade. Accordingly, the 103 lesions were divided in two subgroups: the tumors of histological grade Ⅰ, Ⅱ (low histological grade) and tumors of grade III (high histological grade); tumors of nuclear grade Ⅰ,Ⅱ (low nuclear grade) and tumors of grade Ⅲ (high nuclear grade). All the tumors were divided into mass-like type and non mass-like type according the enhanced morphology, as well as size ≤20 mm type and size >20 mm type respectively. Correlations between parameters and enhanced morphology, tumor size, histological grade, nuclear grade were analyzed through Mann-Whitney U test, the correlation between the tumor size and quantitative parameters was tested with Spearman correlation. Results Mean Ktrans was higher in tumors with mass-liketumors (n=92) than with non mass-like tumors(n=28), and the differences was statistically significant (P 0.05). There was no significant differences between tumor size≤20 mm(n=40) and size>20 mm (n=52) in mean Ktrans ,kep and ve respectively (P>0.05) .The mean maximal size of mass-like tumors was (2.38±0.95) cm, and there was no significant correlations between the tumors size and Ktrans (r=0.238, P=0.038), kep and ve (r values were 0.223 and 0.070, respectively, P values were 0.052 and 0.547 respectively) . Mean Ktrans, kep was higher in tumors with a high histological grade (n=22) than with a low histological grade(n=52), also was higher in tumors with a high nuclear grade(n=15) than with a low nuclear grade (n=56), with statistically significant differences (P 0.05). Conclusion There is correlation between parameters obtained from DCE-MRI and prognostic factors of breast cancers, with higher Ktrans and kep, or lower ve, indicating poor prognostic factors. Key words: Breast neoplasms; Magnetic resonance imaging; Prognostic factors

Advanced diffusion models in head and neck squamous cell carcinoma patients: Goodness of fit, relationships among diffusion parameters and comparison with dynamic contrast-enhanced perfusion

PurposeWe assessed advanced fitting models of diffusion weighted imaging (DWI) in head/neck squamous cell carcinoma (HNSCC) patients to determine the best goodness of fit and correlations among diffusion parameters. We compared these results with those of dynamic contrast-enhanced (DCE) perfusion parameters. Materials and methodsWe retrospectively evaluated 32 HNSCC patients (12 sinonasal, 20 pharynx/oral cavity). The DWI acquisition used single-shot spin-echo echo-planar imaging (EPI) with 12 b-values (0−2000). We calculated 14 DWI parameters using mono-exponential, bi-exponential, and tri-exponential models, stretched exponential model (SEM) and diffusion kurtosis imaging (DKI) models. We compared each model's goodness of fit using the residual sum of squares (RSS), Akaike Information Criterion (AIC) and Bayesian information criterion (BIC) value. We determined the correlation between each pair of DWI parameters and between each DWI parameter and DCE perfusion parameter. ResultsThe tri-exponential fit's RSS, AIC and BIC values were significantly smaller than those for bi-exponential fit. The RSS, AIC and BIC values of the SEM fit and DKI fit were significantly smaller than mono-exponential model. Significant correlations were observed in 30 pairs (sinonasal cavity) and 31 (sinonasal cavity group) among 91 DWI parameter combinations. Significant correlations were also observed in nine pairs (both sinonasal cavity and pharynx/oral cavity group) among 64 DWI/DCE perfusion parameter pairs, in particular, high positive correlations between the tri-exponential model's intermediate diffusion fraction (f2) and the volume of the extracellular extravascular space per unit volume of tissue (ve) were observed in both patient groups. ConclusionWe identified several correlations between DWI parameters by advanced fitting models and correlations between DWI and DCE parameters. These will help determine HNSCC patients' detailed tissue structures.

Reduction of Longitudinal Vertebral Blood Perfusion and Its Likely Causes: A Quantitative Dynamic Contrast-enhanced MR Imaging Study of a Rat Osteoporosis Model.

Purpose To determine the longitudinal relationships among lumbar vertebral blood perfusion, bone mass, and marrow adipose tissue in a rat osteoporosis model after ovariectomy by using quantitative dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging, microcomputed tomography (micro-CT), and proton MR spectroscopy. Materials and Methods In this animal review committee-approved study, lumbar vertebrae were evaluated through MR spectroscopy, quantitative DCE MR imaging, micro-CT, and histopathologic analysis, and blood was examined at 0, 2, 6, 10, 14, 18, and 24 weeks after ovariectomy consisting of exposure of the ovaries but no excision (n = 35) or sham operation, defined as exposure of the ovaries but no excision (n = 35). Differences in the parameters of these examinations between two groups at the same time point were analyzed by an independent-sample t test. Results Significantly reduced volume transfer constant (Ktrans) and volume of extravascular extracellular space per unit volume of tissue (week 2 and 10, respectively; P = .036 and P = .014, respectively), decreased bone mineral density (week 2; P = .014), and increased fat fraction (week 6; P = .036) in the ovariectomy group were observed, compared with those in the sham group. Vascular endothelial growth factor and microvessel density values of the ovariectomy group decreased significantly compared with those of the sham group from weeks 18 (P = .005) and 14 (P = .018), respectively. Transmission electron microscopy revealed tighter gaps among vascular endothelial cells and more marrow fibrosis in the ovariectomy group. Conclusion Quantitative DCE MR imaging can directly reflect marrow perfusion. Ktrans is a promising parameter to demonstrate early reduced marrow perfusion. Enhanced vasoconstriction and tightened gaps among vascular endothelial cells may be the likely causes in the initial stage of osteoporosis. Increased marrow adipose tissue, decreased microvessel density, and increased marrow fibrosis may aggravate marrow ischemia in the late stage of osteoporosis. © RSNA, 2016 Online supplemental material is available for this article.

Short-term follow-up MRI after unplanned resection of malignant soft-tissue tumours; quantitative measurements on dynamic contrast enhanced and diffusion-weighted MR images.

To determine the diagnostic availability of dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MR images for evaluating residual tumours at short-term follow-up after unplanned excision of malignant soft-tissue tumours. From January 2013 to September 2014, 38 patients underwent first follow-up MRI, including DCE and DW imaging (DWI), within 3 months of unplanned malignant soft-tissue tumour excision. The presence or absence of definite nodule formation, focal fluid/haematoma collection, oedema and fascial thickening around or at tumour beds were evaluated using conventional MR images. The volume transfer constant between blood plasma and extracellular/extravascular space (EES) (Ktrans), rate constant between EES and blood plasma (Kep), volume of EES space per unit volume of tissue and initial area under the concentration curve (iAUC) values with time-concentration curve (TCC) plots were obtained on DCE images, and apparent diffusion coefficient (ADC) values were measured on ADC maps. All data were statistically analyzed. Of the 21 patients who underwent re-excision, 12 patients had a residual tumor and 9 did not. All conventional MRI variables, except definite nodule formation, were insignificantly related to the presence of residual tumour. However, ADC values were found to be significantly associated with the presence of residual tumour, as were the DCE MRI variables, Ktrans, Kep and iAUC. In particular, TCC pattern and Kep were most significantly associated with residual tumour. Additional DCE images may be useful for determining the presence of residual tumours in tumour beds during short-term follow-up after inadequate malignant soft-tissue tumour excision. The addition of DCE MRI and quantitative analysis of the images obtained might be useful for determining the presence of residual tumour in a tumour bed during short-term follow-up after inadequate excision of a malignant soft-tissue tumour, although DWI was also found to be helpful.

Application of Blood-Brain Barrier Permeability Imaging in Global Cerebral Edema

Blood-brain barrier permeability is not routinely evaluated in the clinical setting. Global cerebral edema occurs after SAH and is associated with BBB disruption. Detection of global cerebral edema using current imaging techniques is challenging. Our purpose was to apply blood-brain barrier permeability imaging in patients with global cerebral edema by using extended CT perfusion. Patients with SAH underwent CTP in the early phase after aneurysmal rupture (days 0-3) and were classified as having global cerebral edema or nonglobal cerebral edema using established noncontrast CT criteria. CTP data were postprocessed into blood-brain barrier permeability quantitative maps of PS (permeability surface-area product), K(trans) (volume transfer constant from blood plasma to extravascular extracellular space), Kep (washout rate constant of the contrast agent from extravascular extracellular space to intravascular space), VE (extravascular extracellular space volume per unit of tissue volume), VP (plasmatic volume per unit of tissue volume), and F (plasma flow) by using Olea Sphere software. Mean values were compared using t tests. Twenty-two patients were included in the analysis. Kep (1.32 versus 1.52, P < .0001), K(trans) (0.15 versus 0.19, P < .0001), VP (0.51 versus 0.57, P = .0007), and F (1176 versus 1329, P = .0001) were decreased in global cerebral edema compared with nonglobal cerebral edema while VE (0.81 versus 0.39, P < .0001) was increased. Extended CTP was used to evaluate blood-brain barrier permeability in patients with SAH with and without global cerebral edema. Kep is an important indicator of altered blood-brain barrier permeability in patients with decreased blood flow, as Kep is flow-independent. Further study of blood-brain barrier permeability is needed to improve diagnosis and monitoring of global cerebral edema.

Apparent Diffusion Coefficient and Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Pancreatic Cancer

To clarify diffusion and perfusion abnormalities and evaluate correlation between apparent diffusion coefficient (ADC), MR perfusion and histopathologic parameters of pancreatic cancer (PC). Eighteen patients with PC underwent diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Parameters of DCE-MRI and ADC of cancer and non-cancerous tissue were compared. Correlation between the rate constant that represents transfer of contrast agent from the arterial blood into the extravascular extracellular space (K, volume of the extravascular extracellular space per unit volume of tissue (Ve), and ADC of PC and histopathologic parameters were analyzed. The rate constant that represents transfer of contrast agent from the extravascular extracellular space into blood plasma, K, tissue volume fraction occupied by vascular space, and ADC of PC were significantly lower than nontumoral pancreases. Ve of PC was significantly higher than that of nontumoral pancreas. Apparent diffusion coefficient and K values of PC were negatively correlated to fibrosis content and fibroblast activation protein staining score. Fibrosis content was positively correlated to Ve. Apparent diffusion coefficient values and parameters of DCE-MRI can differentiate PC from nontumoral pancreases. There are correlations between ADC, K, Ve, and fibrosis content of PC. Fibroblast activation protein staining score of PC is negatively correlated to ADC and K. Apparent diffusion coefficient, K, and Ve may be feasible to predict prognosis of PC.

Signal intensity-time curve and quantitative dynamic contrast-enhanced magnetic resonance imaging in differentiating neoplasms of uterus

To evaluate signal intensity-time (SI-Time) curve and quantitative dynamic contrast-enhanced 3.0T magnetic resonance imaging in diagnosis and differentiating neoplasm of uterus. A total of 42 cases of uterine neoplasm (20 were malignant and 22 were benign) were evaluated in our study. All cases received dynamic contrast-enhanced scanning on 3.0T MRI. The raw data was processed by Siemens Tissue 4D software and the SI-Time curve was obtained and analyzed. Pharmacokinetic modeling of Tofts with a modeled vascular input function was used for calculating volume parameters: volume transfer constant (Ktrans), reverse volume transfer constant (Kep), the extravascular extracellular space volume per unit volume of tissue (Ve). The correlation of these parameters at each groups were investigated. The SI-Time curve and the data of perfusion parameters between the 2 groups were compared by T test. Among 20 malignant tumors, 12 were cervical carcinoma and 8 were endometrial cancer. Among the benign tumors, 13 were leiomyomas, 3 were endometrial polyp, 3 were endometrial hyperplasia, and 3 were adenomyosis. 59.1% cases of benign tumors belong to Type I curve and 65% cases of malignant tumors belong to Type II curve. There was significant difference in SI-Time curve between benign and malignant tumors (P=0.011). If Type I curve was used as diagnostic criteria for benign tumors, and Type II and III curve were for malignant tumors, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value were 90.0%, 59.1%, 66.7%, and 86.7%, respectively. Ve was 0.477 ± 0.143 in malignant and 0.614 ± 0.146 in control group with significant difference (P=0.004). Ve was 0.477 ± 0.143 in malignant and 0.589 0.176 in benign group with significant difference (P=0.004). Ktrans was (0.178 ± 0.067) min⁻¹ in malignant and (0.263 ± 0.111) min⁻¹ in control group with significant difference (P=0.003). Ktrans was (0.182 ± 0.096) min⁻¹ in benign and (0.263 ± 0.111) min⁻¹ in control group with significant difference (P=0.011). The type of SI-Time curve and perfusion parameters were important for differentiating benign and malignant uterine tumors in dynamic enhanced MRI. These parameters provide a supplement for conventional morphological MR diagnosis.

Sunflower: a potential fructan-bearing crop?

Grain filling in sunflower (Helianthus annuus L.) mainly depends on actual photosynthesis, being the contribution of stored reserves in stems (sucrose, hexoses, and starch) rather low. Drought periods during grain filling often reduce yield. Increasing the capacity of stem to store reserves could help to increase grain filling and yield stability in dry years. Fructans improve water uptake in soils at low water potential, and allow the storage of large amount of assimilates per unit tissue volume that can be readily remobilized to grains. Sunflower is a close relative to Jerusalem artichoke (H. tuberosus L.), which accumulates large amounts of fructan (inulin) in tubers and true stems. The reason why sunflower does not accumulate fructans is obscure. Through a bioinformatics analysis of a sunflower transcriptome database, we found sequences that are homologous to dicotyledon and monocotyledon fructan synthesis genes. A HPLC analysis of stem sugar composition revealed the presence of low amounts of 1-kestose, while a drastic enhancement of endogenous sucrose levels by capitulum removal did not promote 1-kestose accumulation. This suggests that the regulation of fructan synthesis in this species may differ from the currently best known model, mainly derived from research on Poaceae, where sucrose acts as both a signaling molecule and substrate, in the induction of fructan synthesis. Thus, sunflower might potentially constitute a fructan-bearing species, which could result in an improvement of its performance as a grain crop. However, a large effort is needed to elucidate how this up to now unsuspected potential could be effectively expressed.

DNA Yield From Tissue Samples in Surgical Pathology and Minimum Tissue Requirements for Molecular Testing.

Complex molecular assays are increasingly used to direct therapy and provide diagnostic and prognostic information but can require relatively large amounts of DNA. To provide data to pathologists to help them assess tissue adequacy and provide prospective guidance on the amount of tissue that should be procured. We used slide-based measurements to establish a relationship between processed tissue volume and DNA yield by A260 from 366 formalin-fixed, paraffin-embedded tissue samples submitted for the 3 most common molecular assays performed in our laboratory (EGFR, KRAS, and BRAF). We determined the average DNA yield per unit of tissue volume, and we used the distribution of DNA yields to calculate the minimum volume of tissue that should yield sufficient DNA 99% of the time. All samples with a volume greater than 8 mm(3) yielded at least 1 μg of DNA, and more than 80% of samples producing less than 1 μg were extracted from less than 4 mm(3) of tissue. Nine square millimeters of tissue should produce more than 1 μg of DNA 99% of the time. We conclude that 2 tissue cores, each 1 cm long and obtained with an 18-gauge needle, will almost always provide enough DNA for complex multigene assays, and our methodology may be readily extrapolated to individual institutional practice.

The assessment of immature microvascular density in brain gliomas with dynamic contrast-enhanced magnetic resonance imaging

PurposeThis study was designed to quantitatively evaluate the immature microvascular density (MVD) of brain gliomas using the volume transfer constant (Ktrans) and volume of extravascular extracellular space per unit volume of tissue (Ve) from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) noninvasively. Materials and methodsFifty-seven patients (35 males, 22 females; age range, 14–70, mean age 46±12 years old) with brain glioma were included in this study. The maximal values of Ktrans and Ve of all patients with brain glioma (grade II 24, III 7 and IV 26) were obtained. The CD105-microvascular density (CD105-MVD) of each tumor was measured in surgical specimen. The differences of Ktrans, Ve and CD105-MVD between the different grades of gliomas were analyzed using the Mann–Whitney U-test. The Pearman correlation coefficient was determined between Ktrans, Ve and CD105-MVD. A P-value of less than 0.05 was considered statistically significant. ResultsThe differences in Ktrans, Ve and CD105-MVD were statistically significant between low-grade glioma (LGG) and high-grade glioma (HGG) (P=0.001, P<0.001, P<0.001). The Ktrans, Ve and CD105-MVD of grade II were significantly lower than those of grade III and IV. Ktrans and Ve were positively correlated with CD105-MVD in HGG (P<0.001, P<0.001). ConclusionsOur results suggest DCE-MRI plays an important part in noninvasively evaluating the immature MVD of brain gliomas.