Dosimetric impact of the positioning variation of tumor treating field electrodes in the PriCoTTF-phase I/II trial.

PURPOSE: The aim of the present study based on the PriCoTTF-phase I/II trial is the quantification of skin-normal tissue complication probabilities of patients with newly diagnosed glioblastoma multiforme treated with Tumor Treating Field (TTField) electrodes, concurrent radiotherapy, and temozolomide. Furthermore, the skin-sparing effect by the clinically applied strategy of repetitive transducer array fixation around their center position shall be examined. MATERIAL AND METHODS: Low-dose cone-beam computed tomography (CBCT) scans of all fractions of the first seven patients of the PriCoTTF-phase I/II trial, used for image guidance, were applied for the dosimetric analysis, for precise TTField transducer array positioning and contour delineation. Within this trial, array positioning was varied from fixation-to-fixation period with a standard deviation of 1.1 cm in the direction of the largest variation of positioning and 0.7 cm in the perpendicular direction. Physical TTField electrode composition was examined and a respective Hounsfield Unit attributed to the TTField electrodes. Dose distributions in the planning CT with TTField electrodes in place, as derived from prefraction CBCTs, were calculated and accumulated with the algorithm Acuros XB. Dose-volume histograms were obtained for the first and second 2 mm scalp layer with and without migrating electrodes and compared with those with fixed electrodes in an average position. Skin toxicity was quantified according to Lyman's model. Minimum doses in hot-spots of 0.05 cm2 and 25 cm2 ( Δ D0.05cm 2 , Δ D25cm 2 ) size in the superficial skin layers were analyzed. RESULTS: Normal tissue complication probabilities (NTCPs) for skin necrosis ranged from 0.005% to 1.474% (median 0.111%) for the different patients without electrodes. NTCP logarithms were significantly dependent on patient (P < 0.0001) and scenario (P < 0.0001) as classification variables. Fixed positioning of TTField arrays increased skin-NTCP by a factor of 5.50 (95%, CI: 3.66-8.27). The variation of array positioning increased skin-NTCP by a factor of only 3.54 (95%, CI: 2.36-5.32) (P < 0.0001, comparison to irradiation without electrodes; P = 0.036, comparison to irradiation with fixed electrodes). NTCP showed a significant rank correlation with D25cm2 over all patients and scenarios (rs  = 0.76; P < 0.0001). CONCLUSION: Skin-NTCP calculation uncovers significant interpatient heterogeneity and may be used to stratify patients into high- and low-risk groups of skin toxicity. Array position variation may mitigate about one-third of the increase in surface dose and skin-NTCP by the TTField electrodes.

Evaluation of pharmacokinetic models for perfusion imaging with dynamic contrast-enhanced magnetic resonance imaging in porcine skeletal muscle using low-molecular-weight contrast agents.

PURPOSE: Pharmacokinetic models for perfusion quantification with a low-molecular-weight contrast agent (LMCA) in skeletal muscle using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were evaluated. METHODS: Tissue perfusion was measured in seven regions of interest (ROIs) placed in the total hind leg supplied by the femoral artery in seven female pigs. DCE-MRI was performed using a 3D gradient echo sequence with k-space sharing. The sequence was acquired twice, first after LMCA and then after blood pool contrast agent injection. Blood flow was augmented by continuous infusion of the vasodilator adenosine into the femoral artery, resulting in up to four times increased blood flow. The results obtained with several LMCA models were compared with those of a two-compartment blood pool model (2CBPM) consisting of a capillary and an arteriolar compartment. Measurements performed with a Doppler flow probe placed at the femoral artery served as ground truth. RESULTS: The two-compartment exchange model extended by an arteriolar compartment (E2CXM) showed the highest fit quality of all LMCA models and the most significant correlation with the Doppler measurements, r = 0.78 (P < 0.001). The best correspondence between the capillary perfusion measurements of the LMCA models and those of the 2CBPM was found with the E2CXM (slope of the regression line equal to 1, r = 0.85, P < 0.001). The results for the clinical patient data corresponded very well with the results obtained in the animal experiments. CONCLUSIONS: Double-contrast agent DCE-MRI in combination with the E2CXM yields the most reliable results and can be used in clinical routine. Magn Reson Med 79:3154-3162, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Gd-EOB-DTPA-enhanced MRI for monitoring future liver remnant function after portal vein embolization and extended hemihepatectomy: A prospective trial.

OBJECTIVES: To evaluate changes in liver function after right portal vein embolization (PVE) and extended right hemihepatectomy using gadolinium ethoxybenzyl-DTPA-enhanced (Gd-EOB-DTPA) MRI. METHODS: In this prospective trial, 37 patients undergoing PVE were examined before and 14 and 28 days after PVE and 10 days after extended hemihepatectomy using Gd-EOB-DTPA-enhanced MRI. Lobar volume, kinetic growth rate (KGR), relative enhancement (RE) as well as hepatocellular uptake index (HUI) and fat signal fraction (FSF) were calculated for each lobe. RESULTS: RE of the left liver lobe (LLL) was steadily increasing after PVE and decreased to 0.48 ± 0.19 10 days after surgery, which is significantly lower than 14 days and 28 days post PVE (P < 0.05). KGR was 14.06 ± 9.82%/week for the period from PVE to 14 days after PVE. HUI of the LLL increased steadily after PVE and was significantly higher at both 14 and 28 days after PVE compared to pre PVE (P < 0.05). HUI of the residual liver after surgery was lower than before. CONCLUSIONS: Gd-EOB-DTPA-enhanced MRI may be used to monitor the functional increase in the FLR after PVE and to depict the intraoperative liver injury leading to a decrease in liver remnant function. KEY POINTS: • The most significant FLR volume increase happens within the first 14 days. • No MRI parameter was able to predict the success of FLR growth. • Our data suggest an early resection about 14 days after PVE. • Routine Gd-EOB-DTPA-enhanced MRI might be suitable to replace ICG-test.

Does IIH Alter Brain Microstructures? - A DTI-Based Approach.

INTRODUCTION: To investigate the correlation of microstructural parameters with CSF pressure and macroscopic changes assessed by diffusion tensor imaging (DTI) in patients with idiopathic intracranial hypertension (IIH). METHODS: Twenty-three patients with IIH as well as age-, sex-, and body mass index (BMI)-matched controls underwent high resolution MR imaging of the optic nerve sheaths (ONS), pituitary gland, and ventricles. For DTI data a voxelwise permutation analysis was performed for the whole brain and ROI analysis was performed for the optic nerve and optic radiation. DTI measurements were correlated to morphometric measurements, CSF opening pressure, and headache intensity. The reliability of diagnostic performance of DTI parameters was assessed using ROC analysis. RESULTS: Analysis of DTI metrics revealed a significant reduction in the fractional anisotropy (FA) of the optic nerve in patients with IIH. In contrast, systematic regional variations between IIH patients and controls were neither observed in the whole brain analysis nor in the optic radiation. FA values of the optic nerve show significant correlations with the optic nerve sheath diameter (P = .003, r = -.589). The correlation of the alterations of the FA values of the optic radiation and the whole brain do not show a significant association to morphometric alterations in the ONS diameter and hypophysis height as well as to CSF opening pressure and headache intensity. CONCLUSIONS: The results indicate that IIH is associated with microstructural changes in the optic nerve. These alterations may be the direct consequence of chronically elevated intracranial pressure.

Imaging-based evaluation of liver function: comparison of 99mTc-mebrofenin hepatobiliary scintigraphy and Gd-EOB-DTPA-enhanced MRI.

OBJECTIVES: To compare Gd-EOB-enhanced MRI and (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests for separate evaluation of right (RLL) and left liver lobe (LLL) function. METHODS: Fourteen patients underwent Gd-EOB-enhanced MRI and (99m)Tc-mebrofenin HBS after portal vein embolization within 24 h. Relative enhancement (RE) and hepatic uptake index (HUI) were determined from MRI; and T max, T 1/2 and mebrofenin uptake were determined from HBS, all values separately for RLL and LLL. RESULTS: Mebrofenin uptake correlated significantly with HUI and RE for both liver lobes. There was strong correlation of mebrofenin uptake with HUI for RLL (r (2) = 0.802, p = 0.001) and RE for LLL (r (2) = 0.704, p = 0.005) and moderate correlation with HUI for LLL (r (2) = 0.560, p = 0.037) and RE for RLL (r (2) = 0.620, p = 0.018). Correlating the percentage share of RLL function derived from MRI (with HUI) with the percentage of RLL function derived from mebrofenin uptake revealed a strong correlation (r (2) = 0.775, p = 0.002). CONCLUSIONS: Both RE and HUI correlate with mebrofenin uptake in HBS. The results suggest that Gd-EOB-enhanced MRI and (99m)Tc-mebrofenin HBS may equally be used to separately determine right and left liver lobe function. KEY POINTS: • Information about liver function can be acquired with routine Gd-EOB-MRI. • Gd-EOB-MRI and (99m) Tc-mebrofenin HBS show elevated function of non-embolized lobe. • Gd-EOB-MRI and (99m) Tc-mebrofenin HBS can determine lobar liver function.

Evaluation of gadolinium-EOB-DTPA uptake after portal vein embolization: value of an increased flip angle.

BACKGROUND: The optimal sequence for Gd-EOB-DTPA uptake measurement in the liver with the purpose of liver function measurement is still not defined. PURPOSE: To prospectively evaluate the effect of an increased flip angle (FA) of a T1-weighted fat-saturated 3D sequence for the measurement of hepatocyte uptake of Gd-EOB-DTPA magnetic resonance imaging (MRI) after right portal vein embolization (PVE). MATERIAL AND METHODS: Ten patients who received a PVE prior to an extended hemihepatectomy were examined 14 days after PVE using Gd-EOB-DTPA enhanced MRI of the liver using the standard FA of 10° and the increased FA of 30°. RESULTS: Relative enhancement of the right liver lobe (RLL) was 0.52 ± 0.12 for 10° and 1.41 ± 0.39 for 30°. Relative enhancement of the left liver lobe (LLL) was 0.58 ± 0.11 for 10° and 2.05 ± 0.61 for 30°. Relative enhancement of the RLL was significantly higher for 30° than for 10° (P = 0.009) and significantly higher in the 30° than in the 10° sequences (P = 0.005) for the LLL. CONCLUSION: A flip angle of 30° increases the contrast between liver partitions with and without portal venous embolization. Thereby, the sensitivity for differences in uptake intensity is increased. This could be of value for a more exact determination of differences in regional liver function and, consequently, the estimation of the future remnant liver function.

Increase in left liver lobe function after preoperative right portal vein embolisation assessed with gadolinium-EOB-DTPA MRI.

OBJECTIVES: To prospectively evaluate the early development of regional liver function after right portal vein embolisation (PVE) with Gd-EOB-DTPA-enhanced MRI in patients scheduled for extended right hemihepatectomy. METHODS: Ten patients who received a PVE before an extended hemihepatectomy were examined before and 14 days after PVE using Gd-EOB-DTPA-enhanced MRI of the liver. In these sequences representative region of interest measurements were performed in the embolised right (RLL) and the non-embolised left liver lobe (LLL). The volume as well as hepatic uptake index (HUI) was calculated independently for each lobe. RESULTS: Relative enhancement 14 days after PVE decreased in the RLL and increased significantly in the LLL (P < 0.05). Average hepatic uptake index (HUI) for RLL was significantly lower 14 days after PVE than before PVE (P < 0.05) and significantly higher for LLL (P < 0.05). CONCLUSIONS: A significant shift of contrast uptake from the right to the left liver lobe can be depicted as early as 14 days after right PVE by using Gd-EOB-DTPA-enhanced MRI, which could reflect the redirected portal venous blood flow and the rapid utilisation of a hepatic functional reserve. KEY POINTS: • Preoperative portal vein embolisation (PVE) is widely performed before right-sided hepatic resection. • PVE increases intravenous contrast medium uptake in the left lobe of liver. • The hepatic uptake index for the left liver lobe increases rapidly after PVE. • Left liver lobe function increase may be visualised by Gd-EOB-DTPA-enhanced MRI.

Optimal length and temporal resolution of dynamic contrast-enhanced MR imaging for the differentiation between prostate cancer and normal peripheral zone tissue.

The value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the detection of prostate cancer is controversial. There are currently insufficient peer reviewed published data or expert consensus to support routine adoption of DCE-MRI for clinical use. Thus, the objective of this study was to explore the optimal temporal resolution and measurement length for DCE-MRI to differentiate cancerous from normal prostate tissue of the peripheral zone of the prostate by non-parametric MRI analysis and to compare with a quantitative MRI analysis. Predictors of interest were onset time, relative signal intensity (RSI), wash-in slope, peak enhancement, wash-out and wash-out slope determined from non-parametric characterisation of DCE-MRI intensity-time profiles. The discriminatory power was estimated from C-statistics based on cross validation. We analyzed 54 patients with 97 prostate tissue specimens (47 prostate cancer, 50 normal prostate tissue) of the peripheral zone, mean age 63.8 years, mean prostate-specific antigen 18.9 ng/mL and mean of 10.5 days between MRI and total prostatectomy. When comparing prostate cancer tissue with normal prostate tissue, median RSI was 422% vs 330%, and wash-in slope 0.870 vs 0.539. The peak enhancement of 67 vs 42 was higher with prostate cancer tissue, while wash-out (-30% vs -23%) and wash-out slope (-0.037 vs -0.029) were lower, and the onset time (32 seconds) was comparable. The optimal C-statistics was 0.743 for temporal resolution of 8.0 seconds and measurement length of 2.5 minutes compared with 0.656 derived from a quantitative MRI analysis. This study provides evidence that the use of a non-parametric approach instead of a more established parametric approach resulted in greater precision to differentiate cancerous from normal prostate tissue of the peripheral zone of the prostate.

Breast cancer: early- and late-fluorescence near-infrared imaging with indocyanine green--a preliminary study.

PURPOSE: To assess early- and late-fluorescence near-infrared imaging, corresponding to the vascular (early-fluorescence) and extravascular (late-fluorescence) phases of indocyanine green (ICG) enhancement, for breast cancer detection and benign versus malignant breast lesion differentiation. MATERIALS AND METHODS: The study was approved by the ethical review board; all participants provided written informed consent. Twenty women with 21 breast lesions were examined with near-infrared imaging before, during, and after intravenous injection of ICG. Absorption and fluorescence projection mammograms were recorded simultaneously on a prototype near-infrared imaging unit. Two blinded readers independently assessed the images and assigned visibility scores to lesions seen on the absorption and absorption-corrected fluorescence mammograms. Imaging results were compared with histopathologic findings. Lesion contrast and diameter on the fluorescence mammograms were measured, and Cohen κ, Mann-Whitney U, and Spearman ρ tests were conducted. RESULTS: The absorption-corrected fluorescence ratio mammograms showed high contrast (contrast value range, 0.25-0.64) between tumors and surrounding breast tissue. Malignant lesions were correctly defined in 11 (reader 1) and 12 (reader 2) of 13 cases, and benign lesions were correctly defined in six (reader 1) and five (reader 2) of eight cases with late-fluorescence imaging. Lesion visibility scores for malignant and benign lesions were significantly different on the fluorescence ratio mammograms (P = .003) but not on the absorption mammograms (P = .206). Mean sensitivity and specificity reached 92% ± 8 (standard error of mean) and 75% ± 16, respectively, for fluorescence ratio imaging compared with 100% ± 0 and 25% ± 16, respectively, for conventional mammography alone. CONCLUSION: Preliminary data suggest that early- and late-fluorescence ratio imaging after ICG administration can be used to distinguish malignant from benign breast lesions.

Monte Carlo simulation of contrast-enhanced whole brain radiotherapy on a CT scanner.

PURPOSE: To perform a feasibility study of contrast-enhanced whole brain radiotherapy for treating patients with multiple brain metastasis using a conventional computed tomography (CT) scanner. METHODS: The treatment dose was optimized to be applied in a single run using a maximum tube power of 5200 kWs at 140 kV. CT scans of a large and a small head were used as reference. Irradiation geometry, shielding, axial beam collimation, radial beam collimation, gantry tilt, and tube current for beam modulation were optimized using a Monte Carlo simulation and a contrast agent concentration of 5 mg/ml iodine in the tumor. The statistical uncertainty of the Monte Carlo simulation was corrected using back convolution. RESULTS: Using a CT tube with a beam collimation of 28.8 mm, a mean tumor dose of 1.76 +/- 0.13 Gy was achieved, while the head bone dose was 2.61 +/- 0.18 Gy with a normal brain dose of 0.98 +/- 0.06 Gy, eye dose of 0.19 +/- 0.05 Gy, and lens dose of 0.15 +/- 0.03 Gy, respectively. Using a CT tube with dose modulation and a beam collimation of 40.0 mm, the mean tumor dose was 2.00 +/- 0.11 Gy with a head bone dose of 1.96 +/- 0.14 Gy, normal brain dose of 1.13 +/- 0.08 Gy, eye dose of 0.21 +/- 0.05 Gy, and lens dose of 0.16 +/- 0.02 Gy, respectively. Thus a standard CT scanner enables an effective tumor dose of 37.0 Gy to be administered in 13 fractions, while exposing healthy brain to an effective dose of 17.2 Gy and head bone to 69.3 Gy. Additional radial collimation implemented in the hardware improves the therapeutic tumor dose by 25.2% in relation to the bone dose. CONCLUSIONS: Contrast-enhanced total brain radiotherapy is feasible using a conventional CT tube with optimized dose application.

Fractional calculus tracer kinetic compartment model for quantification of microvascular perfusion.

Objective. We evaluate a tracer kinetic model for quantification of physiological perfusion and microvascular residue time kurtosis (RTK) in skeletal muscle vasculature with first pass bolus experiments in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).Approach. A decreasing stretched Mittag-Leffler function (f1C model) was obtained as the impulse response solution of a rate equation of real-valued ('fractional') derivation order. The method was validated in skeletal muscle in the lower limb of seven female pigs examined by DCE-MRI. Dynamic imaging during blood pool contrast agent elimination was performed using a 3D gradient echo sequence with k-space sharing. Blood flow was augmented by continuous infusion of the vasodilator adenosine into the femoral artery increasing blood flow up to four times. Blood flow measured by a Doppler flow probe placed at the femoral artery served as ground truth.Main results. Goodness of fit and correlation with the Doppler measurements,r= 0.80 (P< 0.001), of the 4-parameter f1C model was comparable with the results obtained with a previously tested 6-parameter two-compartment (2C) model. The derivation orderαof the f1C model can be interpreted as a measure of microvascular RTK. With increasing blood flow,αdropped significantly, leading to an increase in RTK.Significance. The f1C model is a practical approach based on hemodynamic principles to quantify physiological microvascular perfusion but it is impaired due to its compartmental nature.

Differentiation of prostate cancer from normal prostate tissue: role of hotspots in pharmacokinetic MRI and histologic evaluation.

OBJECTIVE: The purpose of this study was to investigate whether analysis of voxels with the highest perfusion and blood volume (hotspots) within a whole region affected by prostate cancer can improve differentiation of cancerous and normal prostate tissue at pharmacokinetic MRI. SUBJECTS AND METHODS: Fifty-three patients with biopsy-proven prostate cancer were examined with 1.5-T MRI performed with endorectal and body phased-array coils and a dynamic contrast-enhanced inversion-prepared dual-contrast gradient-echo sequence (temporal resolution, 1.65 seconds). Perfusion and blood volume maps were generated with a sequential three-compartment model. A total of 110 regions (62 prostate cancer, 48 normal prostate tissue) and their MRI perfusion and blood volume hotspots were analyzed and correlated with histologic mean vessel density and mean vessel area. RESULTS: In patients with prostate cancer, median perfusion in the entire region was 0.71 mL/cm(3)min(-1) (hotspot, 1.53 mL/cm(3)min(-1)) with a median blood volume of 1.06% (hotspot, 2.23%). In the corresponding histologic areas, median mean vessel density was 77 vessels/mm(2) (hotspot, 156 vessels/mm(2)) with a median mean vessel area of 1.61% (hotspot, 2.50%). In normal prostate tissue, median perfusion was 0.33 mL/cm(3)min(-1) (hotspot, 1.38 mL/cm(3)min(-1)) with a median blood volume of 0.62% (hotspot, 2.6%). In the corresponding histologic regions, median mean vessel density in the entire area was 57 vessels/mm(2) with a median mean vessel area of 1.21% (no hotspots). MRI perfusion in the entire region was the most suitable parameter for differentiating prostate cancer and facilitated correct classification in 61.8% of cases (blood volume hotspots, 58.2%; perfusion hotspots, 56.4%). CONCLUSION: In differentiation of cancerous and normal prostate tissue, use of perfusion in the entire region is superior to use of perfusion and blood volume in MRI hotspots.

Non-invasive magnetic resonance thermography during regional hyperthermia.

Regional hyperthermia is a non-invasive technique in which cancer tissue is exposed to moderately high temperatures of approximately 43-45 degrees C. The clinical delivery of hyperthermia requires control of the temperatures applied. This is typically done using catheters with temperature probes, which is an interventional procedure. Additionally, a catheter allows temperature monitoring only at discrete positions. These limitations can be overcome by magnetic resonance (MR) thermometry, which allows non-invasive mapping of the entire treatment area during hyperthermia application. Various temperature-sensitive MRI parameters exist and can be exploited for MR temperature mapping. The most popular parameters are proton resonance frequency shift (PRFS) (Delta phi corresponding to a frequency shift of 0.011 ppm, i.e. 0.7 Hz per degrees C at 1.5 Tesla), diffusion coefficient D (Delta D/D = 2-3 % per degrees C), longitudinal relaxation time T(1) (Delta T1/T1 approximately 1% per degrees C), and equilibrium magnetisation M(0) (Delta M(0)/M=0.3% per degrees C). Additionally, MRI temperature mapping based on temperature-sensitive contrast media is applied. The different techniques of MRI thermometry were developed to serve different purposes. The PRFS method is the most sensitive proton imaging technique. A sensitivity of +/-0.5 degrees C is possible in vivo but use of PRFS imaging remains challenging because of a high sensitivity to susceptibility effects, especially when field homogeneity is poor, e.g. on interventional MR scanners or because of distortions caused by an inserted applicator. Diffusion-based MR temperature mapping has an excellent correlation with actual temperatures in tissues. Correct MR temperature measurement without rescaling is achieved using the T(1) method, if the scaling factor is known. MR temperature imaging methods using exogenous temperature indicators are chemical shift and 3D phase sensitive imaging. TmDOTMA(-) appears to be the most promising lanthanide complex because it showed a temperature imaging accuracy of <0.3 degrees C.

Tumour perfusion assessment during regional hyperthermia treatment: comparison of temperature probe measurement with H(2)(15)O-PET perfusion.

PURPOSE: Hyperthermia treatment might increase tumour oxygenation and perfusion, as has been reported for experimental tumours. The present study was performed to investigate this hypothesis in patients undergoing regional hyperthermia treatment. METHODS: Thirteen patients with primary or recurrent pelvic tumours were included in this study. Prior to and up to one hour after regional hyperthermia, perfusion was quantitatively determined by H(2)(15)O-PET. The fused CT-PET images were used to extract tumour time-activity curves and to identify the catheter position. Perfusion was calculated from the total tumour time-activity curves and for the time-activity curves at the catheter site. Additionally, perfusion was calculated from the temperature-time curves measured using temperature probes. RESULTS: Perfusion values calculated using H(2)(15)O-PET and those deduced from temperature probe measurements are significantly correlated with a correlation coefficient, R = 0.21. The perfusion values deduced from the temperature measured in a body cavity do not provide information about average tumour perfusion. Perfusion values deduced from the temperature are overestimated for very poorly perfused tissues and underestimated for highly perfused tissues. CONCLUSIONS: Temperature measurement during hyperthermia may allow only determination of intermediate perfusion values.

Liver function quantification of patients with portal vein embolization using dynamic contrast-enhanced MRI for assessment of hepatocyte uptake and elimination.

PURPOSE: We evaluated pharmacokinetic models which quantify liver function including biliary elimination based on a dynamic Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) technique with sparse data collection feasible in clinical routine. METHODS: Twelve patients with embolized liver segments following interventional treatment of primary liver cancer or hepatic metastasis underwent MRI. During Gd-EOB-DTPA bolus administration, a 3D dynamic gradient-echo (GRE) MRI examination was performed over approx. 28 min. Interrupted data sampling was started approx. 5 min after contrast agent administration. Different implementations of dual-inlet models were tested, namely the Euler method (DE) and convolution with residue functions (C). A simple uptake model (U) and an uptake- elimination model (UE) extended by incorporating the biliary contrast agent elimination rate (Ke) were evaluated. RESULTS: The uptake-elimination model, calculated via the simple Euler method (UE- DE) and by convolution (UE-C), yielded similar overall estimates in terms of fitting quality and agreement with published values. The Euler method was approx. 50 times faster and yielded a mean elimination rate of Ke=1.8±1.2mL/(min·100 mL) in nonembolized liver tissue, which was significantly higher (p=8.8·10-4) than in embolized tissue Ke=0.4±0.4 mL/(min·100 mL). Fractional hepatocyte volume vh was not significantly higher in nonembolized tissue (52.4 ± 13.4 mL/100 mL) compared to embolized tissue (44.4 ± 26.1 mL/100 mL). CONCLUSIONS: Interrupted late enhancement MRI data sampling in conjunction with the uptake-elimination model, deconvolved by integration of the differential rate equation and combined with the simple uptake model implemented with the Euler method (U-DE), turned out to be a stable and practical method for reliable noninvasive assessment of liver function.

Prostate MR imaging: tissue characterization with pharmacokinetic volume and blood flow parameters and correlation with histologic parameters.

PURPOSE: To prospectively determine whether pharmacokinetic magnetic resonance (MR) imaging parameters correlate with histologic mean vessel density (MVD), mean vessel area (MVA), and mean interstitial area (MIA) and whether these parameters enable differentiation of prostate cancer, chronic prostatitis, and normal prostate tissue. MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was obtained from all patients. Thirty-five patients with biopsy-proved prostate cancer were examined with a dynamic contrast material-enhanced inversion-prepared dual-contrast gradient-echo sequence (temporal resolution, 1.65 seconds) at 1.5 T to calculate blood volume, interstitial volume, and blood flow. These parameters were correlated with MVD, MVA, and MIA in 95 areas (prostate cancer, n = 36; chronic prostatitis, n = 27; normal prostate tissue, n = 32). For each MR area, five 1-mm(2) squares (original magnification, x100) of the matching histologic area were analyzed. The Wilcoxon signed-rank test was used for statistical analysis. RESULTS: Blood volume correlated poorly with MVD (Spearman correlation coefficient, 0.252; P = .014) but did not correlate at all with MVA (P = .759). Interstitial volume did not correlate with MIA (P = .507). Blood volume differed between patients with prostate cancer and those with a normal prostate (1.49% vs 0.84%, respectively; P < .001). Interstitial volume differed between patients with chronic prostatitis and those with a normal prostate (39.00% vs 22.59%, respectively; P = .022). Blood flow differed between patients with prostate cancer and those with a normal prostate (0.97 mL/[cm(3) x min(-1)] vs 0.34 mL/[cm(3) x min(-1)], respectively; P < .001), between patients with prostate cancer and those with chronic prostatitis (0.97 mL/[cm(3) x min(-1)] vs 0.60 mL/[cm(3) x min(-1)], respectively; P = .026), and between patients with chronic prostatitis and those with a normal prostate (0.60 mL/[cm(3) x min(-1)] vs 0.34 mL/[cm(3) x min(-1)], respectively; P = .023). CONCLUSION: Blood volume and interstitial volume did not reliably correlate with the histologic parameters. Only blood flow enabled differentiation of prostate cancer, chronic prostatitis, and normal prostate tissue.

Photoelectric-enhanced radiation therapy with quasi-monochromatic computed tomography.

Photoelectric-enhanced radiation therapy is a bimodal therapy, consisting of the administration of highly radiation-absorbing substances into the tumor area and localized regional irradiation with orthovoltage x-rays. Irradiation can be performed by a modified computed tomography (CT) unit equipped with an additional x-ray optical module which converts the polychromatic, fan-shaped CT beam into a monochromatized and focused beam for energy-tuned photoelectric-enhanced radiotherapy. A dedicated x-ray optical module designed for spatial collimation, focusing, and monochromatization was mounted at the exit of the x-ray tube of a clinical CT unit. Spectrally resolved measurements of the resulting beam were performed using an energy-dispersive detection system calibrated by synchrotron radiation. The spatial photon fluence was determined by film dosimetry. Depth-dose measurements were performed and compared to the polychromatic CT and a therapeutic 6 MV beam. The spatial dose distribution in phantoms using a rotating radiation source (quasimonochromatic CT and 6 MV, respectively) was investigated by gel dosimetry. The photoelectric dose enhancement for an iodine fraction of 1% in tissue was calculated and verified experimentally. The x-ray optical module selectively filters the energy of the tungsten Kalpha emission line with an FWHM of 5 keV. The relative photon fluence distribution demonstrates the focusing characteristic of the x-ray optical module. A beam width of about 3 mm was determined at the isocenter of the CT gantry. The depth-dose measurements resulted in a half-depth value of approximately 36 mm for the CT beams (quasi-monochromatic, polychromatic) compared to 154 mm for the 6 MV beam. The rotation of the radiation source leads to a steep dose gradient at the center of rotation; the gel dosimetry yields an entrance-to-peak dose ratio of 1:10.8 for the quasi-monochromatic CT and 1:37.3 for a 6 MV beam of the same size. The photoelectric dose enhancement factor increases from 2.2 to 2.4 by using quasi-monochromatic instead of polychromatic radiation. An additional increase in the radiation dose by a factor of 1.4 due to the focusing characteristic of the x-ray optical module was calculated. Photoelectric-enhanced radiation therapy based on a clinical CT unit combined with an x-ray optical module is a novel therapy option in radiation oncology. The optimized quasi-monochromatic radiation is strongly focused and ensures high photoelectric dose enhancement for iodine.

Combined morphological and functional liver MRI using spin-lattice relaxation in the rotating frame (T1ρ) in conjunction with Gadoxetic Acid-enhanced MRI.

Noninvasive early detection of liver cirrhosis and fibrosis is essential for management and therapy. The aim was to investigated whether a combination of the functional parameter relative enhancement (RE) on Gadoxetic Acid magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) and the fibrosis parameter T1ρ distinguishes cirrhosis and healthy liver. We analyzed patients with Gd-EOB-DTPA-enhanced MRI and T1ρ mapping. Signal intensity was measured before and after contrast; RE was calculated. T1ρ was measured with circular regions of interest (T1ρ-cROI). A quotient of RE and T1ρ-cROI was calculated: the fibrosis function quotient (FFQ). Cirrhosis was evaluated based on morphology and secondary changes. 213 datasets were included. The difference between cirrhotic and noncirrhotic liver was 51.11 ms vs. 47.56 ms for T1ρ-cROI (p < 0.001), 0.59 vs. 0.70 for RE (p < 0.001), and 89.53 vs. 70.83 for FFQ (p < 0.001). T1ρ-cROI correlated with RE, r = -0.14 (p < 0.05). RE had an AUC of 0.73. The largest AUC had the FFQ with 0.79. The best cutoff value was 48.34 ms for T1ρ-cROI, 0.70 for RE and 78.59 ms for FFQ. In conclusion T1ρ and RE can distinguish between cirrhotic and noncirrhotic liver. The FFQ, which is the combination of the two, improves diagnostic performance.

Simultaneous multislice acquisition with multi-contrast segmented EPI for separation of signal contributions in dynamic contrast-enhanced imaging.

We present a method to efficiently separate signal in magnetic resonance imaging (MRI) into a base signal S0, representing the mainly T1-weighted component without T2*-relaxation, and its T2*-weighted counterpart by the rapid acquisition of multiple contrasts for advanced pharmacokinetic modelling. This is achieved by incorporating simultaneous multislice (SMS) imaging into a multi-contrast, segmented echo planar imaging (EPI) sequence to allow extended spatial coverage, which covers larger body regions without time penalty. Simultaneous acquisition of four slices was combined with segmented EPI for fast imaging with three gradient echo times in a preclinical perfusion study. Six female domestic pigs, German-landrace or hybrid-form, were scanned for 11 minutes respectively during administration of gadolinium-based contrast agent. Influences of reconstruction methods and training data were investigated. The separation into T1- and T2*-dependent signal contributions was achieved by fitting a standard analytical model to the acquired multi-echo data. The application of SMS yielded sufficient temporal resolution for the detection of the arterial input function in major vessels, while anatomical coverage allowed perfusion analysis of muscle tissue. The separation of the MR signal into T1- and T2*-dependent components allowed the correction of susceptibility related changes. We demonstrate a novel sequence for dynamic contrast-enhanced MRI that meets the requirements of temporal resolution (Δt < 1.5 s) and image quality. The incorporation of SMS into multi-contrast, segmented EPI can overcome existing limitations of dynamic contrast enhancement and dynamic susceptibility contrast methods, when applied separately. The new approach allows both techniques to be combined in a single acquisition with a large spatial coverage.