Exploring the Neural Mechanisms of Mirrored-Self Misidentification in Alzheimer's Disease.

OBJECTIVE: Alzheimer's disease (AD) is a complex neurodegenerative condition that causes a range of cognitive disturbances, including mirror-self misidentification syndrome (MSM), in which patients cannot recognize themselves in a mirror. However, the mechanism of action of MSM is not precisely known. This study aimed to explore the possible neural mechanisms of action of MSM in AD using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: This study included 48 AD patients, 13 in the MSM group and 35 in the non-MSM group. The permeability of the blood-brain barrier (BBB) was quantitatively monitored by measuring the transfer rate (Ktrans) of the contrast agent from the vasculature to the surrounding tissue using DCE-MRI. The concentration of contrast agents in different brain regions was measured, and the Patlak model was used to calculate Ktrans. Ktrans values were compared between the left and right cerebral hemispheres in different brain areas between the MSM and non-MSM groups. Additionally, the difference in Ktrans values between mild and severe MSM was assessed. Logistic regression analysis was used to examine the risk factors for MSM. RESULTS: The Mann‒Whitney U test was used to compare two groups and revealed elevated Ktrans values in the left thalamus, left putamen, left globus pallidus, left corona radiata, and right caudate in the MSM group (p < 0.05). Logistic regression analysis revealed that increased Ktrans values in the left putamen (OR = 1.53, 95% CI = 1.04, 2.26) and left globus pallidus (OR = 1.54, 95% CI = 1.02, 2.31) may be risk factors for MSM. After dividing MSM patients into mild and moderate-severe groups, the Ktrans values of the thalamus in the moderate-severe group were greater than those in the mild group (p < 0.05). CONCLUSION: Our study revealed the relationship between BBB permeability and MSM in AD. MSM is associated with BBB breakdown in the left putamen and globus pallidus. The left putamen and globus pallidus may function in mirror self-recognition. Higher BBB permeability in the thalamus may reflect the severity of AD in MSM.

Diagnosis and monitoring denosumab therapy of giant cell tumors of bone: radiologic-pathologic correlation.

OBJECTIVE: To determine the value of CT and dynamic contrast-enhanced (DCE-)MRI for monitoring denosumab therapy of giant cell tumors of bone (GCTB) by correlating it to histopathology. MATERIALS AND METHODS: Patients with GCTB under denosumab treatment and monitored with CT and (DCE-)MRI (2012-2021) were retrospectively included. Imaging and (semi-)quantitative measurements were used to assess response/relapse. Tissue samples were analyzed using computerized segmentation for vascularization and number of neoplastic and giant cells. Pearson's correlation/Spearman's rank coefficient and Kruskal-Wallis tests were used to assess correlations between histopathology and radiology. RESULTS: Six patients (28 ± 8years; five men) were evaluated. On CT, good responders showed progressive re-ossification (+7.8HU/month) and cortical remodeling (woven bone). MRI showed an SI decrease relative to muscle on T1-weighted (-0.01 A.U./month) and on fat-saturated T2-weighted sequences (-0.03 A.U./month). Time-intensity-curves evolved from a type IV with high first pass, high amplitude, and steep wash-out to a slow type II. An increase in time-to-peak (+100%) and a decrease in Ktrans (-71%) were observed. This is consistent with microscopic examination, showing a decrease of giant cells (-76%), neoplastic cells (-63%), and blood vessels (-28%). There was a strong statistical significant inverse correlation between time-to-peak and microvessel density (ρ = -0.9, p = 0.01). Significantly less neoplastic (p = 0.03) and giant cells (p = 0.04) were found with a time-intensity curve type II, compared to a type IV. Two patients showed relapse after initial good response when stopping denosumab. Inverse imaging and pathological findings were observed. CONCLUSION: CT and (DCE-)MRI show a good correlation with pathology and allow adequate evaluation of response to denosumab and detection of therapy failure.

Quantitative DCE-MRI prediction of breast cancer recurrence following neoadjuvant chemotherapy: a preliminary study.

INTRODUCTION: Breast cancer patients treated with neoadjuvant chemotherapy (NACT) are at risk of recurrence depending on clinicopathological characteristics. This preliminary study aimed to investigate the predictive performances of quantitative dynamic contrast-enhanced (DCE) MRI parameters, alone and in combination with clinicopathological variables, for prediction of recurrence in patients treated with NACT. METHODS: Forty-seven patients underwent pre- and post-NACT MRI exams including high spatiotemporal resolution DCE-MRI. The Shutter-Speed model was employed to perform pharmacokinetic analysis of the DCE-MRI data and estimate the Ktrans, ve, kep, and τi parameters. Univariable logistic regression was used to assess predictive accuracy for recurrence for each MRI metric, while Firth logistic regression was used to evaluate predictive performances for models with multi-clinicopathological variables and in combination with a single MRI metric or the first principal components of all MRI metrics. RESULTS: Pre- and post-NACT DCE-MRI parameters performed better than tumor size measurement in prediction of recurrence, whether alone or in combination with clinicopathological variables. Combining post-NACT Ktrans with residual cancer burden and age showed the best improvement in predictive performance with ROC AUC = 0.965. CONCLUSION: Accurate prediction of recurrence pre- and/or post-NACT through integration of imaging markers and clinicopathological variables may help improve clinical decision making in adjusting NACT and/or adjuvant treatment regimens to reduce the risk of recurrence and improve survival outcome.

Imaging acute effects of bevacizumab on tumor vascular kinetics in a preclinical orthotopic model of U251 glioma.

The effect of a human vascular endothelial growth factor antibody on the vasculature of human tumor grown in rat brain was studied. Using dynamic contrast-enhanced magnetic resonance imaging, the effects of intravenous bevacizumab (Avastin; 10 mg/kg) were examined before and at postadministration times of 1, 2, 4, 8, 12 and 24 h (N = 26; 4-5 per time point) in a rat model of orthotopic, U251 glioblastoma (GBM). The commonly estimated vascular parameters for an MR contrast agent were: (i) plasma distribution volume (vp ), (ii) forward volumetric transfer constant (Ktrans ) and (iii) reverse transfer constant (kep ). In addition, extracellular distribution volume (VD ) was estimated in the tumor (VD-tumor ), tumor edge (VD-edge ) and the mostly normal tumor periphery (VD-peri ), along with tumor blood flow (TBF), peri-tumoral hydraulic conductivity (K) and interstitial flow (Flux) and tumor interstitial fluid pressure (TIFP). Studied as % changes from baseline, the 2-h post-treatment time point began showing significant decreases in vp , VD-tumor, VD-edge and VD-peri , as well as K, with these changes persisting at 4 and 8 h in vp , K, VD-tumor, -edge and -peri (t-tests; p < 0.05-0.01). Decreases in Ktrans were observed at the 2- and 4-h time points (p < 0.05), while interstitial volume fraction (ve ; = Ktrans /kep ) showed a significant decrease only at the 2-h time point (p < 0.05). Sustained decreases in Flux were observed from 2 to 24 h (p < 0.01) while TBF and TIFP showed delayed responses, increases in the former at 12 and 24 h and a decrease in the latter only at 12 h. These imaging biomarkers of tumor vascular kinetics describe the short-term temporal changes in physical spaces and fluid flows in a model of GBM after Avastin administration.

Dynamic contrast-enhanced magnetic resonance imaging in correlation with tongue cancer stages.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) plays a significant role in tumor stage as it can be used to measure tissue perfusion and permeability of tumors. PURPOSE: To investigate the relationships between both quantitative and semi-quantitative variables obtained from DCE-MRI and tongue cancer stages. MATERIAL AND METHODS: Mean values of Ktrans, enhancement ratio (ER), wash-in slope (slope), and the 95th percentile (95%) values of the distribution for Ktrans, ER, and slope values (Ktrans (95%), ER (95%), and slope (95%), respectively) were calculated for 53 patients with tongue cancers (American Joint Committee on Cancer 8th Edition stage group: 10 in stages I and II, 14 in stage III, 21 in stage IVa, and eight in stage IVb as determined by histopathologic assessment). The relationship between tumor staging and each of the six DCE-MRI parameters was assessed separately using ordinal logistic regression. RESULTS: The logistic regression analysis revealed that both mean and 95th percentile values of Ktrans were significantly and positively correlated with tongue cancer stage (P < 0.01). More aggressive tumor stages had larger kinetic parameter. Moreover, the semi-quantitative parameters, such as ER (95%) and slope (95%), may be more significant predictors for evaluating tongue cancer stages than the mean ER and mean slope. CONCLUSION: Both quantitative and semi-quantitative imaging biomarkers are useful for evaluating the stages of tongue cancer, and the indices obtained from DCE-MRI were positively correlated with the tumor stages. These parameters have the potential to non-invasively evaluate the stages of tongue cancer in the clinical setting.

Role of Various DW MRI and DCE MRI Parameters as Predictors of Malignancy in Solid Pulmonary Lesions.

PURPOSE: We aimed to evaluate various diffusion and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) parameters in differentiating malignant from benign pulmonary lesions. METHODS: We enrolled 31 (22 males) patients who had solid pulmonary lesion(s) >2 cm in our cross sectional study. Of these, 23 (74.2%) were found to be malignant on histopathology. Dynamic contrast-enhanced MRI was performed using 36 dynamic measurements (volumetric interpolated breath-hold examination). Diffusion-weighted MRI (DW MRI) performed at b value of 800 s/mm2. We measured different diffusion and perfusion parameters, for example, diffusion-weighted imaging (DWI) SI, mean apparent diffusion coefficient (ADC), minimum ADC, lesion-to-spinal cord ratio, DWI score, T2 score, Ktrans, Kep, and Ve. We stratified values of each parameter as high if it was >median of values observed in our data set and low if it was ≤median. Normally distributed data were compared by unpaired t test, whereas non-normal continuous data were compared by Kruskal Wallis-H test. We applied Wilson score method to calculate sensitivity, specificity, and predictive values of parameters that were statistically significant by type of lesion with reference to histopathological examination as gold standard. RESULTS: Diffusion-weighted imaging SI, mean ADC, minimum ADC, DWI score and Ktrans values were found to be significantly different (P value < .05) by type of lesion. Ktrans was found to have the highest diagnostic accuracy (74.2%) among these parameters. CONCLUSION: Ktrans and mean ADC had similar sensitivity of 65.2%. However, Ktrans had highest diagnostic accuracy among various DWI and DCE MRI parameters in predicting malignancy in solid pulmonary lesions. In our study, we found a cutoff value 0.251 min-1 for Ktrans as 100% specific.

Dynamic contrast-enhanced magnetic resonance imaging perfusion characteristics in meningiomas treated with resection and adjuvant radiosurgery.

OBJECTIVEThere is a need for advanced imaging biomarkers to improve radiation treatment planning and response assessment. T1-weighted dynamic contrast-enhanced perfusion MRI (DCE MRI) allows quantitative assessment of tissue perfusion and blood-brain barrier dysfunction and has entered clinical practice in the management of primary and secondary brain neoplasms. The authors sought to retrospectively investigate DCE MRI parameters in meningiomas treated with resection and adjuvant radiation therapy using volumetric segmentation.METHODSA retrospective review of more than 300 patients with meningiomas resected between January 2015 and December 2018 identified 14 eligible patients with 18 meningiomas who underwent resection and adjuvant radiotherapy. Patients were excluded if they did not undergo adjuvant radiation therapy or DCE MRI. Demographic and clinical characteristics were obtained and compared to DCE perfusion metrics, including mean plasma volume (vp), extracellular volume (ve), volume transfer constant (Ktrans), rate constant (kep), and wash-in rate of contrast into the tissue, which were derived from volumetric analysis of the enhancing volumes of interest.RESULTSThe mean patient age was 64 years (range 49-86 years), and 50% of patients (7/14) were female. The average tumor volume was 8.07 cm3 (range 0.21-27.89 cm3). The median Ki-67 in the cohort was 15%. When stratified by median Ki-67, patients with Ki-67 greater than 15% had lower median vp (0.02 vs 0.10, p = 0.002), and lower median wash-in rate (1.27 vs 4.08 sec-1, p = 0.04) than patients with Ki-67 of 15% or below. Logistic regression analysis demonstrated a statistically significant, moderate positive correlation between ve and time to progression (r = 0.49, p < 0.05). Furthermore, there was a moderate positive correlation between Ktrans and time to progression, which approached, but did not reach, statistical significance (r = 0.48, p = 0.05).CONCLUSIONSThis study demonstrates a potential role for DCE MRI in the preoperative characterization and stratification of meningiomas, laying the foundation for future prospective studies incorporating DCE as a biomarker in meningioma diagnosis and treatment planning.

Impact of contrast agent injection duration on dynamic contrast-enhanced MRI quantification in prostate cancer.

The volume transfer constant Ktrans , which describes the leakage of contrast agent (CA) from vasculature into tissue, is the most commonly reported quantitative parameter for dynamic contrast-enhanced (DCE-) MRI. However, the variation in reported Ktrans values between studies from different institutes is large. One of the primary sources of uncertainty is quantification of the arterial input function (AIF). The aim of this study is to determine the influence of the CA injection duration on the AIF and tracer kinetic analysis (TKA) parameters (i.e. Ktrans , kep and ve ). Thirty-one patients with prostate cancer received two DCE-MRI examinations with an injection duration of 5 s in the first examination and a prolonged injection duration in the second examination, varying between 7.5 s and 30 s. The DCE examination was carried out on a 3.0 T MRI scanner using a transversal T1 -weighted 3D spoiled gradient echo sequence (300 s duration, dynamic scan time of 2.5 s). Data of 29 of the 31 were further analysed. AIFs were determined from the phase signal in the left and right femoral arteries. Ktrans , kep and ve were estimated with the standard Tofts model for regions of healthy peripheral zone and tumour tissue. We observed a significantly smaller peak height and increased width in the AIF for injection durations of 15 s and longer. However, we did not find significant differences in Ktrans , kep or ve for the studied injection durations. The study demonstrates that the TKA parameters Ktrans , kep and ve , measured in the prostate, do not show a significant change as a function of injection duration.

Dynamic contrast-enhanced and diffusion-weighted MR imaging in the characterisation of small, non-palpable solid testicular tumours.

OBJECTIVES: To explore the role of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), using semiquantitative and quantitative parameters, and diffusion-weighted (DW) MRI in differentiating benign from malignant small, non-palpable solid testicular tumours. METHODS: We calculated the following DCE-MRI parameters of 47 small, non-palpable solid testicular tumours: peak enhancement (PE), time to peak (TTP), percentage of peak enhancement (Epeak), wash-in-rate (WIR), signal enhancement ratio (SER), volume transfer constant (Ktrans), rate constant (Kep), extravascular extracellular space volume fraction (Ve) and initial area under the curve (iAUC). DWI signal intensity and apparent diffusion coefficient (ADC) values were evaluated. RESULTS: Epeak, WIR, Ktrans , Kep and iAUC were higher and TTP shorter in benign compared to malignant lesions (p < 0.05). All tumours had similar ADC values (p > 0.07). Subgroup analysis limited to the most frequent histologies - Leydig cell tumours (LCTs) and seminomas - replicated the findings of the entire set. Best diagnostic cutoff value for identification of seminomas: Ktrans ≤0.135 min-1, Kep ≤0.45 min-1, iAUC ≤10.96, WIR ≤1.11, Epeak ≤96.72, TTP >99 s. CONCLUSIONS: DCE-MRI parameters are valuable in differentiating between benign and malignant small, non-palpable testicular tumours, especially when characterising LCTs and seminomas. KEY POINTS: • DCE-MRI may be used to differentiate benign from malignant non-palpable testicular tumours. • Seminomas show lower Ktrans, Kep and iAUC values. • ADC values are not valuable in differentiating seminomas from LCTs. • Semiquantitative DCE-MRI may be used to characterise small, solid testicular tumours.

The quantification of blood-brain barrier disruption using dynamic contrast-enhanced magnetic resonance imaging in aging rhesus monkeys with spontaneous type 2 diabetes mellitus.

Microvascular lesions of the body are one of the most serious complications that can affect patients with type 2 diabetes mellitus. The blood-brain barrier (BBB) is a highly selective permeable barrier around the microvessels of the brain. This study investigated BBB disruption in diabetic rhesus monkeys using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Multi-slice DCE-MRI was used to quantify BBB permeability. Five diabetic monkeys and six control monkeys underwent magnetic resonance brain imaging in 3 Tesla MRI system. Regions of the frontal cortex, the temporal cortex, the basal ganglia, the thalamus, and the hippocampus in the two groups were selected as regions of interest to calculate the value of the transport coefficient Ktrans using the extended Tofts model. Permeability in the diabetic monkeys was significantly increased as compared with permeability in the normal control monkeys. Histopathologically, zonula occludens protein-1 decreased, immunoglobulin G leaked out of the blood, and nuclear factor E2-related factor translocated from the cytoplasm to the nuclei. It is likely that diabetes contributed to the increased BBB permeability.

DCE- and DW-MRI as early imaging biomarkers of treatment response in a preclinical model of triple negative breast cancer.

This work evaluates quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted MRI (DW-MRI) parameters as early biomarkers of response in a preclinical model of triple negative breast cancer (TNBC). The standard Tofts' model of DCE-MRI returns estimates of the volume transfer constant (Ktrans ) and the extravascular extracellular volume fraction (ve ). DW-MRI returns estimates of the apparent diffusion coefficient (ADC). Mice (n = 38) were injected subcutaneously with MDA-MB-231. Tumors were grown to approximately 275 mm3 and sorted into the following groups: saline controls, low-dose Abraxane (15 mg/kg) and high-dose Abraxane (25 mg/kg). Animals were imaged at days zero, one and three. On day three, tumors were extracted for immunohistochemistry. The positive percentage change in ADC on day one was significantly higher in both treatment groups relative to the control group (p < 0.05). In addition, the positive percentage change in Ktrans was significantly higher than controls (p < 0.05) on day one for the high-dose group and on days one and three for the low-dose group. The percentage change in tumor volume was significantly different between the high-dose and control groups on day three (p = 0.006). Histology confirmed differences at day three through reduced numbers of proliferating cells (Ki67 staining) in the high-dose group (p = 0.03) and low-dose group (p = 0.052) compared with the control group. Co-immunofluorescent staining of vascular maturity [using von Willebrand Factor (vWF) and α-smooth muscle actin (α-SMA)] indicated significantly higher vascular maturation in the low-dose group compared with the controls on day three (p = 0.03), and trending towards significance in the high-dose group compared with controls on day three (p = 0.052). These results from quantitative imaging with histological validation indicate that ADC and Ktrans have the potential to serve as early biomarkers of treatment response in murine studies of TNBC.

Biopsy targeting with dynamic contrast-enhanced versus standard neuronavigation MRI in glioma: a prospective double-blinded evaluation of selection benefits.

Current biopsy planning based on contrast-enhanced T1W (CET1W) or FLAIR sequences frequently delivers biopsy samples that are not in concordance with the gross tumor diagnosis. This study investigates whether the quantitative information of transfer constant Ktrans maps derived from T1W dynamic contrast-enhanced MRI (DCE-MRI) can help enhance the quality of biopsy target selection in glioma. 28 patients with suspected glioma received MRI including DCE-MRI and a standard neuronavigation protocol of 3D FLAIR- and CET1W data sets (0.1 mmol/kg gadobutrol) at 3.0 T. After exclusion of five cases with no Ktrans-elevation, 2-6 biopsy targets were independently selected by a neurosurgeon (samples based on standard imaging) and a neuroradiologist (samples based on kinetic parameter Ktrans) per case and tissue samples corresponding to these targets were collected by a separate independent neurosurgeon. Standard technique and Ktrans-based samples were rated for diagnostic concordance with the gross tumor resection reference diagnosis (67 WHO IV; 24 WHO III and II) by a neuropathologist blinded for selection mode. Ktrans-based sample targets differed from standard technique sample targets in 90/91 cases. More Ktrans-based than standard imaging-based samples could be extracted. Diagnoses from Ktrans-based samples were more frequently concordant with the reference gross tumor diagnoses than those from standard imaging-based samples (WHO IV: 30/39 vs. 11/20; p = 0.08; WHO III/II: 12/13 vs. 6/11; p = 0.06). In 4/5 non-contrast-enhancing gliomas, Ktrans-based selection revealed significantly more accurate samples than standard technique sample-selection (10/12 vs. 2/8 samples; p = 0.02). If Ktrans elevation is present, Ktrans-based biopsy targeting provides significantly more diagnostic tissue samples in non-contrast-enhancing glioma than selection based on CET1W and FLAIR-weighted images alone.

Limited accuracy of DCE-MRI in identification of pathological complete responders after chemoradiotherapy treatment for rectal cancer.

OBJECTIVES: To examine whether post-chemoradiotherapy (CRT) DCE-MRI can identify rectal cancer patients with pathologic complete response (pCR). METHODS: From a rectal cancer surgery database 2007-2014, 61 consecutive patients that met the following inclusion criteria were selected for analysis: (1) stage II/III primary rectal adenocarcinoma; (2) received CRT; (3) underwent surgery (4); underwent rectal DCE-MRI on a 1.5-T MRI scanner. Two experienced radiologists, in consensus, drew regions of interest (ROI) on the sagittal DCE-MRI image in the tumour bed. These were exported from ImageJ to in-house Matlab code for modelling using the Tofts model. K trans, K ep and v e values were compared to pathological response. RESULTS: Of the 61 initial patients, 37 had data considered adequate for fitting to obtain perfusion parameters. Among the 13 men and 24 women, median age 53 years, there were 8 pCR (22 %). K trans could not distinguish patients with pCR. For patients with 90 % or greater response, mean K trans and K ep values were statistically significant (p = 0.032 and 0.027, respectively). Using a cutoff value of K trans = 0.25 min-1, the AUC was 0.71. CONCLUSION: K trans could be used to identify patients with 90 % or more response to chemoradiotherapy for rectal cancer with an AUC of 0.7. KEY POINTS: • Chemoradiotherapy for rectal cancer causes decreased blood flow and permeability in the tumour bed. • Lower values of blood flow and permeability correlate with good tumour response. • K trans of 0.25min -1 best identifies patients with ≥90 % response with AUC 0.71.

Dynamic contrast enhanced MR imaging for evaluation of angiogenesis of hepatocellular nodules in liver cirrhosis in N-nitrosodiethylamine induced rat model.

PURPOSE: To investigate whether dynamic contrast -enhanced MRI (DCE-MRI) can distinguish the type of liver nodules in a rat model with N-nitrosodiethylamine- induced cirrhosis. METHODS: Liver nodules in cirrhosis were induced in 60 male Wistar rats via 0.01 % N-nitrosodiethylamine in the drinking water for 35-100 days. The nodules were divided into three groups: regenerative nodule (RN), dysplastic nodule (DN), and hepatocellular carcinoma (HCC). DCE-MRI was performed, and parameters including transfer constant (Ktrans), rate constant (Kep), extravascular extracellular space volume fraction (Ve), and initial area under the contrast concentration versus time curve (iAUC) were measured and compared. RESULTS: The highest Ktrans and iAUC values were seen in HCC, followed by DN and RN (all P < 0.05). The area under the receiver operating characteristic curve (AUROC) for DN and HCC were 0.738 and 0.728 for Ktrans and iAUC, respectively. The AUROC for HCC were 0.850 and 0.840 for Ktrans and iAUC, respectively. Ordinal logistic regression analysis showed that Ktrans had a high goodness of fit (0.970, 95 % confidence interval, 13.751-24.958). CONCLUSION: DCE-MRI is a promising method to differentiate of liver nodules. Elevated Ktrans suggested that the nodules may be transformed into HCC. KEY POINTS: • DCE-MRI is promising for differentiating among RN, DN, and HCC • K trans and iAUC positively correlated with malignancy degree of liver nodules • Elevated K trans suggests that the nodules may be transformed into HCC.

Dynamic contrast-enhanced magnetic resonance imaging of osseous spine metastasis before and 1 hour after high-dose image-guided radiation therapy.

OBJECTIVE High-dose image-guided radiation therapy (HD IGRT) has been instrumental in mitigating some limitations of conventional RT. The recent emergence of dynamic contrast-enhanced (DCE) MRI to investigate tumor physiology can be used to verify the response of human tumors to HD IGRT. The purpose of this study was to evaluate the near-immediate effects of HD IGRT on spine metastases through the use of DCE MRI perfusion studies. METHODS Six patients with spine metastases from prostate, thyroid, and renal cell carcinoma who underwent HD IGRT were studied using DCE MRI prior to and 1 hour after HD IGRT. The DCE perfusion parameters plasma volume (Vp) and vascular permeability (Ktrans) were measured to assess the near-immediate and long-term tumor response. A Mann-Whitney U-test was performed to compare significant changes (at p ≤ 0.05) in perfusion parameters before and after RT. RESULTS The authors observed a precipitous drop in Vp within 1 hour of HD IGRT, with a mean decrease of 65.2%. A significant difference was found between Vp values for before and 1 hour after RT (p ≤ 0.05). No significant change was seen in Vp (p = 0.31) and Ktrans (p = 0.1) from 1 hour after RT to the first follow-up. CONCLUSIONS The data suggest that there is an immediate effect of HD IGRT on the vascularity of spine metastases, as demonstrated by a precipitous decrease in Vp. The DCE MRI studies can detect such changes within 1 hour after RT, and findings are concordant with existing animal models.

Optimal acquisition and modeling parameters for accurate assessment of low Ktrans blood-brain barrier permeability using dynamic contrast-enhanced MRI.

PURPOSE: To determine optimal parameters for acquisition and processing of dynamic contrast-enhanced MRI (DCE-MRI) to detect small changes in near normal low blood-brain barrier (BBB) permeability. METHODS: Using a contrast-to-noise ratio metric (K-CNR) for Ktrans precision and accuracy, the effects of kinetic model selection, scan duration, temporal resolution, signal drift, and length of baseline on the estimation of low permeability values was evaluated with simulations. RESULTS: The Patlak model was shown to give the highest K-CNR at low Ktrans . The Ktrans transition point, above which other models yielded superior results, was highly dependent on scan duration and tissue extravascular extracellular volume fraction (ve ). The highest K-CNR for low Ktrans was obtained when Patlak model analysis was combined with long scan times (10-30 min), modest temporal resolution (<60 s/image), and long baseline scans (1-4 min). Signal drift as low as 3% was shown to affect the accuracy of Ktrans estimation with Patlak analysis. CONCLUSION: DCE acquisition and modeling parameters are interdependent and should be optimized together for the tissue being imaged. Appropriately optimized protocols can detect even the subtlest changes in BBB integrity and may be used to probe the earliest changes in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis.

Assessment of vessel permeability by combining dynamic contrast-enhanced and arterial spin labeling MRI.

The forward volumetric transfer constant (K(trans)), a physiological parameter extracted from dynamic contrast-enhanced (DCE) MRI, is weighted by vessel permeability and tissue blood flow. The permeability × surface area product per unit mass of tissue (PS) in brain tumors was estimated in this study by combining the blood flow obtained through pseudo-continuous arterial spin labeling (PCASL) and K(trans) obtained through DCE MRI. An analytical analysis and a numerical simulation were conducted to understand how errors in the flow and K(trans) estimates would propagate to the resulting PS. Fourteen pediatric patients with brain tumors were scanned on a clinical 3-T MRI scanner. PCASL perfusion imaging was performed using a three-dimensional (3D) fast-spin-echo readout module to determine blood flow. DCE imaging was performed using a 3D spoiled gradient-echo sequence, and the K(trans) map was obtained with the extended Tofts model. The numerical analysis demonstrated that the uncertainty of PS was predominantly dependent on that of K(trans) and was relatively insensitive to the flow. The average PS values of the whole tumors ranged from 0.006 to 0.217 min(-1), with a mean of 0.050 min(-1) among the patients. The mean K(trans) value was 18% lower than the PS value, with a maximum discrepancy of 25%. When the parametric maps were compared on a voxel-by-voxel basis, the discrepancies between PS and K(trans) appeared to be heterogeneous within the tumors. The PS values could be more than two-fold higher than the K(trans) values for voxels with high K(trans) levels. This study proposes a method that is easy to implement in clinical practice and has the potential to improve the quantification of the microvascular properties of brain tumors.

Reproducibility of DCE-MRI time-intensity curve-shape analysis in patients with knee arthritis: A comparison with qualitative and pharmacokinetic analyses.

PURPOSE: To compare the between-session reproducibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with time-intensity curve (TIC)-shape analysis in arthritis patients, within one scanner and between two different scanners, and to compare this method with qualitative analysis and pharmacokinetic modeling (PKM). MATERIALS AND METHODS: Fifteen knee joint arthritis patients were included and scanned twice on a closed-bore 1.5T scanner (n = 9, group 1), or on a closed-bore 1.5T and on an open-bore 1.0T scanner (n = 6, group 2). DCE-MRI data were postprocessed using in-house developed software ("Dynamo"). Disease activity was assessed. RESULTS: Disease activity was comparable between the two visits. In group 1 qualitative analysis showed the highest reproducibility with intraclass correlation coefficients (ICCs) between 0.78 and 0.98 and root mean square-coefficients of variation (RMS-CoV) of 8.0%-14.9%. TIC-shape analysis showed a slightly lower reproducibility with similar ICCs (0.78-0.97) but higher RMS-CoV (18.3%-42.9%). The PKM analysis showed the lowest reproducibility with ICCs between 0.39 and 0.64 (RMS-CoV 21.5%-51.9%). In group 2 TIC-shape analysis of the two most important TIC-shape types showed the highest reproducibility with ICCs of 0.78 and 0.71 (RMS-CoV 29.8% and 59.4%) and outperformed the reproducibility of the most important qualitative parameter (ICC 0.31, RMS-CoV 45.1%) and the within-scanner reproducibility of PKM analysis. CONCLUSION: TIC-shape analysis is a robust postprocessing method within one scanner, almost as reproducible as the qualitative analysis. Between scanners, the reproducibility of the most important TIC-shapes outperform that of the most important qualitative parameter and the within-scanner reproducibility of PKM analysis.

Intratumor distribution and test-retest comparisons of physiological parameters quantified by dynamic contrast-enhanced MRI in rat U251 glioma.

The distribution of dynamic contrast-enhanced MRI (DCE-MRI) parametric estimates in a rat U251 glioma model was analyzed. Using Magnevist as contrast agent (CA), 17 nude rats implanted with U251 cerebral glioma were studied by DCE-MRI twice in a 24 h interval. A data-driven analysis selected one of three models to estimate either (1) plasma volume (vp), (2) vp and forward volume transfer constant (K(trans)) or (3) vp, K(trans) and interstitial volume fraction (ve), constituting Models 1, 2 and 3, respectively. CA distribution volume (VD) was estimated in Model 3 regions by Logan plots. Regions of interest (ROIs) were selected by model. In the Model 3 ROI, descriptors of parameter distributions--mean, median, variance and skewness--were calculated and compared between the two time points for repeatability. All distributions of parametric estimates in Model 3 ROIs were positively skewed. Test-retest differences between population summaries for any parameter were not significant (p ≥ 0.10; Wilcoxon signed-rank and paired t tests). These and similar measures of parametric distribution and test-retest variance from other tumor models can be used to inform the choice of biomarkers that best summarize tumor status and treatment effects.

Associations between tumor vascularization assessed by in vivo DCE-MRI and the presence of disseminated tumor cells in bone marrow in breast cancer patients at the time of diagnosis.

PURPOSE: To explore possible associations between in vivo pharmacokinetic dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and the presence of disseminated tumor cells (DTCs) in bone marrow in breast cancer patients at the time of diagnosis. MATERIALS AND METHODS: Thirty-seven women with breast cancer (stage T2-4N0-1M0) were included. Patients were classified as DTC+ if one or more DTCs were detected by immunocytochemistry. DCE-MRI was acquired with a radial 3D T1 -weighted spoiled gradient echo sequence with k-space weighted image contrast. K(trans), kep, and ve were calculated using the extended Tofts model and a population-derived arterial input function. The nonparametric Mann-Whitney U-test was used to compare the histogram distributions of the pharmacokinetic parameters for the DTC+ and the DTC- patients. RESULTS: DTCs were detected in 7 of the 37 patients (19%). In DTC+ patients, the distribution of tumor K(trans) and kep were significantly (P < 0.01) more shifted towards lower values than in DTC- patients. CONCLUSION: An association between vascular dependent pharmacokinetic DCE-MRI parameters and the presence of DTCs were found. Compared to DTC- patients, DTC+ patients had poorer perfusion and permeability, indicative of hypoxia. Thus, pharmacokinetic parameters might be surrogate biomarkers of metastatic potential and future relapse.