Neuroendocrine liver metastases treated using transarterial radioembolization: Identification of prognostic parameters at 68Ga-DOTATATE PET/CT.

PURPOSE: To identify prognostic clinical and imaging parameters for patients with neuroendocrine liver metastases (NELMs) undergoing transarterial radioembolization (TARE). MATERIALS AND METHODS: Forty-seven patients (27 men; mean age, 64 years) with NELMs who received TARE, along with pre-procedure liver MRI and 68Ga-DOTATATE positron emission tomography/computed tomography were included. Apparent diffusion coefficient and standardized uptake value (SUV) of three liver metastases, normal spleen and liver were measured. SUVmax or SUVmean were used for the calculation of tumor-to-organ ratios (tumor-to-spleen and tumor-to-liver ratios) using all possible combinations (including SUVmax/SUVmax, SUVmax/SUVmean, and SUVmean/SUVmean). Clinical parameters (hepatic tumor-burden, presence of extra-hepatic metastases, chromograninA, Ki-67 and bilirubin levels) were assessed. Overall survival, progression-free survival (PFS) and hepatic progression-free survival (HPFS) were calculated using Kaplan-Meier curves. RESULTS: Median overall survival, PFS and HPFS were 49.6, 13.1 and 28.3 months, respectively. In multivariable Cox regression analysis, low Ki-67 (≤ 5%), low hepatic tumor-burden (< 10%), absence of extrahepatic metastases, and increased Tmean/Lmax ratio were significant prognostic factors of longer overall survival and HPFS. High baseline chromograninA (> 1330 ng/mL) was associated with shorter HPFS. Tmean/Lmax > 1.9 yielded a median overall survival of 69 vs. 33 months (P < 0.04), and a median HPFS of 30 vs. 19 months (P = 0.09). For PFS, high baseline SUVmax of NELMs was the single significant parameter in the multivariable model. SUVmax > 28 resulted in a median PFS of 16.9 vs. 6.5 months, respectively (P = 0.001). CONCLUSION: High preinterventional Tmean/Lmax ratios, and high SUVmax on 68Ga-DOTATATE positron emission tomography/computed tomography seem to have prognostic value in patients with NELMs undergoing TARE, potentially aiding patient selection and management alongside conventional variables.

Suppression without inhibition: how retinal computation contributes to saccadic suppression.

Visual perception remains stable across saccadic eye movements, despite the concurrent strongly disruptive visual flow. This stability is partially associated with a reduction in visual sensitivity, known as saccadic suppression, which already starts in the retina with reduced ganglion cell sensitivity. However, the retinal circuit mechanisms giving rise to such suppression remain unknown. Here, we describe these mechanisms using electrophysiology in mouse, pig, and macaque retina, 2-photon calcium imaging, computational modeling, and human psychophysics. We find that sequential stimuli, like those that naturally occur during saccades, trigger three independent suppressive mechanisms in the retina. The main mechanism is triggered by contrast-reversing sequential stimuli and originates within the receptive field center of ganglion cells. It does not involve inhibition or other known suppressive mechanisms like saturation or adaptation. Instead, it relies on temporal filtering of the inherently slow response of cone photoreceptors coupled with downstream nonlinearities. Two further mechanisms of suppression are present predominantly in ON ganglion cells and originate in the receptive field surround, highlighting another disparity between ON and OFF ganglion cells. The mechanisms uncovered here likely play a role in shaping the retinal output following eye movements and other natural viewing conditions where sequential stimulation is ubiquitous.

Course of Early Neurologic Symptom Severity after Endovascular Treatment of Anterior Circulation Large Vessel Occlusion Stroke: Association with Baseline Multiparametric CT Imaging and Clinical Parameters.

BACKGROUND: Neurologic symptom severity and deterioration at 24 hours (h) predict long-term outcomes in patients with acute large vessel occlusion (LVO) stroke of the anterior circulation. We aimed to examine the association of baseline multiparametric CT imaging and clinical factors with the course of neurologic symptom severity in the first 24 h after endovascular treatment (EVT). METHODS: Patients with LVO stroke of the anterior circulation were selected from a prospectively acquired consecutive cohort of patients who underwent multiparametric CT, including non-contrast CT, CT angiography and CT perfusion before EVT. The symptom severity was assessed on admission and after 24 h using the 42-point National Institutes of Health Stroke Scale (NIHSS). Clinical and imaging data were compared between patients with and without early neurological deterioration (END). END was defined as an increase in ≥4 points, and a significant clinical improvement as a decrease in ≥4 points, compared to NIHSS on admission. Multivariate regression analyses were used to determine independent associations of imaging and clinical parameters with NIHSS score increase or decrease in the first 24 h. RESULTS: A total of 211 patients were included, of whom 38 (18.0%) had an END. END was significantly associated with occlusion of the internal carotid artery (odds ratio (OR), 4.25; 95% CI, 1.90-9.47) and the carotid T (OR, 6.34; 95% CI, 2.56-15.71), clot burden score (OR, 0.79; 95% CI, 0.68-0.92) and total ischemic volume (OR, 1.01; 95% CI, 1.00-1.01). In a comprehensive multivariate analysis model including periprocedural parameters and complications after EVT, carotid T occlusion remained independently associated with END, next to reperfusion status and intracranial hemorrhage. Favorable reperfusion status and small ischemic core volume were associated with clinical improvement after 24 h. CONCLUSIONS: The use of imaging parameters as a surrogate for early NIHSS progression in an acute LVO stroke after EVT reached limited performance with only carotid T occlusion as an independent predictor of END. Reperfusion status and early complications in terms of intracranial hemorrhage are critical factors that influence patient outcome in the acute stroke phase after EVT.

Performance of implantable loop recorders. Role of R vector and detection algorithms.

INTRODUCTION: We evaluated the performance of implantable loop recorders (ILRs) with different detection algorithms and looked for artifacts and therapeutic consequences and their dependence on patient factors. METHODS AND RESULTS: 586 RevealLinq™ ILRs (first generation (NT): n = 335; second generation with TruRhythm™ (TR): n = 251) were implanted during 2014-2021 (syncope n = 206; embolic stroke of unknown source (ESUS) n = 380). Automatically detected EGM episodes (n = 18,650) were classified as correct or incorrect for asystole (AS), atrial fibrillation (AF) or tachycardia (TA). Incorrect episodes were caused by loss of signal (LO), noise (NO), extrasystole (ES) and T-wave oversensing (TWO). Left directed R axes, lower R-amplitudes and older age were related to artifacts. Results were separated by indication. In ESUS patients TR reduced total median artifact episodes: 0.6 (0-7) vs 0 (0-5) (p < 0.03) and median artifact examination time: 0.3 (0-3.5) vs 0 (0-2.5) (p = 0.03) per patient-year. This benefit is caused by significant reductions in total AS and ES-AS artifacts. The total positive predictive value (PPV) improved only in syncope patients (45 vs 71%, p = 0.002). Accordingly in syncope patients with TR more therapeutic consequences could be established (log rank 0.003). DISCUSSION: Patients R-axis and measured R-amplitudes during implantation predicted artifacts. This should be taken into account during ILR implantation. Total artifacts, AS artifacts and time spent for artifact analysis was reduced by the new TR detection algorithm in ESUS patients, whereas total artifacts remained unchanged in syncope patients despite reduction of AS artifacts. However TR had no effect on AF and TA episode detection and therefore has to be improved.

Bi-Centric Independent Validation of Outcome Prediction after Radioembolization of Primary and Secondary Liver Cancer.

BACKGROUND: Yttrium-90 radioembolization (RE) plays an important role in the treatment of liver malignancies. Optimal patient selection is crucial for an effective and safe treatment. In this study, we aim to validate the prognostic performance of a previously established random survival forest (RSF) with an external validation cohort from a different national center. Furthermore, we compare outcome prediction models with different established metrics. METHODS: A previously established RSF model, trained on a consecutive cohort of 366 patients who had received RE due to primary or secondary liver tumor at a national center (center 1), was used to predict the outcome of an independent consecutive cohort of 202 patients from a different national center (center 2) and vice versa. Prognostic performance was evaluated using the concordance index (C-index) and the integrated Brier score (IBS). The prognostic importance of designated baseline parameters was measured with the minimal depth concept, and the influence on the predicted outcome was analyzed with accumulated local effects plots. RSF values were compared to conventional cox proportional hazards models in terms of C-index and IBS. RESULTS: The established RSF model achieved a C-index of 0.67 for center 2, comparable to the results obtained for center 1, which it was trained on (0.66). The RSF model trained on center 2 achieved a C-index of 0.68 on center 2 data and 0.66 on center 1 data. CPH models showed comparable results on both cohorts, with C-index ranging from 0.68 to 0.72. IBS validation showed more differentiated results depending on which cohort was trained on and which cohort was predicted (range: 0.08 to 0.20). Baseline cholinesterase was the most important variable for survival prediction. CONCLUSION: The previously developed predictive RSF model was successfully validated with an independent external cohort. C-index and IBS are suitable metrics to compare outcome prediction models, with IBS showing more differentiated results. The findings corroborate that survival after RE is critically determined by functional hepatic reserve and thus baseline liver function should play a key role in patient selection.

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization.

BACKGROUND: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8-86.8) vs. 40.2 Gy (12.5-83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 µmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

Cost-Effectiveness Analysis of 68Ga DOTA-TATE PET/CT, 111In-Pentetreotide SPECT/CT and CT for Diagnostic Workup of Neuroendocrine Tumors.

Neuroendocrine tumors (NETs) are relatively rare neoplasms arising from the hormone-producing neuroendocrine system that can occur in various organs such as pancreas, small bowel, stomach and lung. As the majority of these tumors express somatostatin receptors (SSR) on their cell membrane, utilization of SSR analogs in nuclear medicine is a promising, but relatively costly approach for detection and localization. The aim of this study was to analyze the cost-effectiveness of 68Ga-DOTA-TATE PET/CT (Gallium-68 DOTA-TATE Positron emission tomography/computed tomography) compared to 111In-pentetreotide SPECT/CT (Indium-111 pentetreotide Single Photon emission computed tomography/computed tomography) and to CT (computed tomography) alone in detection of NETs. A decision model on the basis of Markov simulations evaluated lifetime costs and quality-adjusted life years (QALYs) related to either a CT, SPECT/CT or PET/CT. Model input parameters were obtained from publicized research projects. The analysis is grounded on the US healthcare system. Deterministic sensitivity analysis of diagnostic parameters and probabilistic sensitivity analysis predicated on a Monte Carlo simulation with 30,000 reiterations was executed. The willingness-to-pay (WTP) was determined to be $ 100,000/QALY. In the base-case investigation, PET/CT ended up with total costs of $88,003.07 with an efficacy of 4.179, whereas CT ended up with total costs of $88,894.71 with an efficacy of 4.165. SPECT/CT ended up with total costs of $89,973.34 with an efficacy of 4.158. Therefore, the strategies CT and SPECT/CT were dominated by PET/CT in the base-case scenario. In the sensitivity analyses, PET/CT remained a cost-effective strategy. This result was due to reduced therapy costs of timely detection. The additional costs of 68Ga-DOTA-TATE PET/CT when compared to CT alone are justified in the light of potential savings in therapy costs and better outcomes.

iRESCUE - Interventional embolization of Renal artEries after SurgiCal or traUmatic injury with hEmorrhage.

OBJECTIVES: To evaluate the efficacy and safety of urgent percutaneous embolization for the treatment of acute renal hemorrhage. MATERIALS AND METHODS: All patients undergoing endovascular embolization at our hospital for bleeding from renal artery branches between January 2010 and June 2020 were retrospectively evaluated. Periprocedural characteristics, technical details, clinical outcomes, and complications were documented. RESULTS: Seventy-six patients with a mean age of 67.3 ± 12.9 underwent 86 procedures. The most common cause of hemorrhage was iatrogenic (63/76), including 44 patients presenting after partial nephrectomy. Bleeding was successfully controlled in 80 of 86 procedures (92.8 % technical success), and clinical success (defined as control of bleeding with endovascular embolization) was achieved in 72 of 76 patients (94.5 %) with embolization, including seven patients undergoing re-intervention. In univariate analysis, risk factors for clinical failure were antiplatelet agents (p = 0.033), and technical failure (p < 0.001); and technical failure was the only significant risk factor in multivariate analysis. Only one patient (1.3 %) needed nephrectomy. AKI was seen after 16 (21 %) procedures, and preprocedural increased creatinine (≧1.8) and decreased GFR (<60) were risk factors for AKI (p = 0.022 and p = 0.020). In all patients except one, renal functions returned to baseline. One patient died because of pulmonary embolism (in-hospital mortality 1.3 %). CONCLUSION: Interventional embolization is feasible, safe, and effective in the treatment of renal hemorrhages. Among others, the complication management with minimally invasive procedures allows urologists to safely perform partial nephrectomy even in patients with central, large, and endophytic tumors, thereby preserving kidney function in these patients.

Advanced Fusion Imaging and Contrast-Enhanced Imaging (CT/MRI-CEUS) in Oncology.

Fusion imaging depicts an innovative technique that facilitates combining assets and reducing restrictions of advanced ultrasound and cross-sectional imaging. The purpose of the present retrospective study was to evaluate the role of fusion imaging for assessing hepatic and renal lesions. Between 02/2011-08/2020, 92 patients in total were included in the study, of which 32 patients had hepatic lesions, 60 patients had renal lesions. Fusion imaging was technically successful in all patients. No adverse side effects upon intravenous (i.v.) application of SonoVue® (Bracco, Milan, Italy) were registered. Fusion imaging could clarify all 11 (100%) initially as indeterminate described hepatic lesions by computed tomography/magnetic resonance imaging (CT/MRI). Moreover, 5/14 (36%) initially suspicious hepatic lesions could be validated by fusion imaging, whereas in 8/14 (57%), malignant morphology was disproved. Moreover, fusion imaging allowed for the clarification of 29/30 (97%) renal lesions initially characterized as suspicious by CT/MRI, of which 19/30 (63%) underwent renal surgery, histopathology revealed malignancy in 16/19 (84%), and benignity in 3/19 (16%). Indeterminate findings could be elucidated by fusion imaging in 20/20 (100%) renal lesions. Its accessibility and repeatability, even during pregnancy and in childhood, its cost-effectiveness, and its excellent safety profile, make fusion imaging a promising instrument for the thorough evaluation of hepatic and renal lesions in the future.

An Unusual Intramolecular Halogen Bond Guides Conformational Selection.

PIK-75 is a phosphoinositide-3-kinase (PI3K) α-isoform-selective inhibitor with high potency. Although published structure-activity relationship data show the importance of the NO2 and the Br substituents in PIK-75, none of the published studies could correctly determine the underlying reason for their importance. In this publication, we report the first X-ray crystal structure of PIK-75 in complex with the kinase GSK-3ß. The structure shows an unusual U-shaped conformation of PIK-75 within the active site of GSK-3ß that is likely stabilized by an atypical intramolecular Br⋅⋅⋅NO2 halogen bond. NMR and MD simulations show that this conformation presumably also exists in solution and leads to a binding-competent preorganization of the PIK-75 molecule, thus explaining its high potency. We therefore suggest that the site-specific incorporation of halogen bonds could be generally used to design conformationally restricted bioactive substances with increased potencies.

Establishing rarity in the context of orphan medicinal product designation in the European Union.

In the European Union (EU) legislative framework for orphan medicinal product designation, establishing that a condition affects not more than five in 10,000 people is a prerequisite for applications based on rarity. Demonstrating this requirement to the Committee of Orphan Medicinal Products (COMP) can be a particularly challenging task for sponsors. Here, we identify and examine three common issues with the estimation of prevalence in orphan drug applications in the EU (the discernment between diagnosed and undiagnosed cases; the duration of the disease; and the need for an explicit contemporary conclusion) as critical factors for acceptable prevalence estimation. These concerns are discussed in detail based on recent examples of applications, which are reflected in published European Medicines Agency (EMA) documents.

Mechanisms of action of Rab proteins, key regulators of intracellular vesicular transport.

Our understanding of the manner in which Rab proteins regulate intracellular vesicular transport has progressed remarkably in the last one or two decades by application of a wide spectrum of biochemical, biophysical and cell biological methods, augmented by the methods of chemical biology. Important additional insights have arisen from examination of the manner in which certain bacteria can manipulate vesicular transport mechanisms. The progress in these areas is summarized here.

Poloxamer-based hydrogels hardening at body core temperature as carriers for cell based therapies: in vitro and in vivo analysis.

Cell-based regenerative therapies for bone defects usually employ bone precursor cells seeded on solid scaffolds. Thermosensitive hydrogels that harden at body core temperature are promising alternative cell carriers as they are applicable minimally invasively. We modified Pluronic® P123 with different chain extenders and assessed rheology and biocompatibility of the resulting hydrogels. The best candidate was tested in a rat's femoral defect model. All gels hardened above 25 °C with butane-diisocyanate-hydrogels (BDI-gels) displaying the highest storage moduli. BDI-gels showed the most favourable biocompatibility and did not affect cellular adipogenic or osteogenic differentiation in vitro. Implantation of BDI-hydrogel into femoral defects did not impede bone healing in vivo as evidenced by µCT and histological analysis. We conclude that thermosensitive BDI-gels are promising alternative cell carriers. The gels harden upon injection in vivo without interfering with bone metabolism. Further experiments will assess the gels' capacity to effectively transport living cells into bone defects.

Diagnostic value of MRI in a pelvic mass of prostatic origin.

We report on the case of a 55-year-old male with acute urinary retention, caused by a large pelvic mass. Contrast enhanced computed tomography showed a vascularized prostatic mass with calcifications. To rule out potential bladder and rectum infiltration and to optimize imaging prior to surgical exploration, an MRI examination including MR angiography and spectroscopy was performed. Clinical findings including intraoperative results are presented in this report in detail and correlated to the results of the state of the art magnetic resonance imaging.

Magnetic resonance imaging of the body trunk using a single-slab, 3-dimensional, T2-weighted turbo-spin-echo sequence with high sampling efficiency (SPACE) for high spatial resolution imaging: initial clinical experiences.

PURPOSE: The authors conducted a clinical evaluation of single-slab, 3-dimensional, T2-weighted turbo-spin-echo (TSE) with high sampling efficiency (SPACE) for high isotropic body imaging with large field-of-view (FoV). MATERIALS AND METHODS: Fifty patients were examined in clinical routine with SPACE (regions of interest: pelvis n=30, lower spine n=12, upper spine n=6, extremities n=4) at 1.5 T. For achieving a high sampling efficiency, parallel imaging, high turbofactor, and magnetization restore pulses were used. In contrast to a conventional TSE imaging technique with constant flip angle refocusing, the refocusing pulse train of the SPACE sequence consists of variable flip angle radiofrequency pulses along the echo train. RESULTS: Signal-to-noise ratio and contrast-to-noise ratio of SPACE images were of sufficient diagnostic value. The possibility of image reconstruction in multiple planes was of clinical relevance in all cases and simplified data analysis. CONCLUSION: The achievement of 3-dimensional, T2-weighted TSE magnetic resonance imaging with isotropic and high spatial resolution and interactive 3-dimensional visualization essentially improve the diagnostic potential of magnetic resonance imaging.

Follow-up gliomas after radiotherapy: 1H MR spectroscopic imaging for increasing diagnostic accuracy.

We evaluated the value of magnetic resonance imaging (MRI) and the additional benefit of proton MR spectroscopic imaging (1H SI) in patients with a new suspicious lesion after fractionated stereotactic radiotherapy (FSRT) of a glioma. Thirty-four patients with histologically proven astrocytoma WHO II-IV after treatment by FSRT and a new suspect lesion in the follow-up were included in this study. Data were analysed by three independent radiologists with different experience in 1H SI: Data were verified by clinical follow-up (PT, progressive tumour; nPT, non-progressive tumour) and a kappa analysis was performed. Sensitivity and specificity of T1 weighted (w) and T2w MRI was compared (imaging at radiotherapy and follow-up) using further follow-up controls as gold standard and the additional benefit of 1H SI (imaging at follow-up) was calculated. Mean interval between last irradiation and detection of a suspicious lesion was 37 +/- 32 months. Time to clinical evaluation was 13 +/- 8 months. Interobserver agreement was significantly high in all analyses (kappa always >0.8, P < 0.05). T2w imaging proved to be superior to contrast enhanced T1w imaging in sensitivity (87.5 vs 81.25%) and specificity (85.7 vs 57.1%). Solitary 1H SI had similar results as T2w (sensitivity 87.5%, specificity 71.4%). Taking all techniques into account, all PT were correctly diagnosed. Radiologists' experience had no significant influence on correct interpretation of a suspicious lesion. We conclude that 1H SI is helpful in characterising new suspicious lesions in irradiated gliomas, particularly if pre-MRI is not available for evaluating follow-up.

Time-resolved contrast-enhanced three-dimensional pulmonary MR-angiography: 1.0 M gadobutrol vs. 0.5 M gadopentetate dimeglumine.

PURPOSE: To compare contrast characteristics and image quality of 1.0 M gadobutrol with 0.5 M Gd-DTPA for time-resolved three-dimensional pulmonary magnetic resonance angiography (MRA). MATERIALS AND METHODS: Thirty-one patients and five healthy volunteers were examined with a contrast-enhanced time-resolved pulmonary MRA protocol (fast low-angle shot [FLASH] three-dimensional, TR/TE = 2.2/1.0 msec, flip angle: 25 degrees, scan time per three-dimensional data set = 5.6 seconds). Patients were randomized to receive either 0.1 mmol/kg body weight (bw) or 0.2 mmol/kg bw gadobutrol, or 0.2 mmol/kg bw Gd-DTPA. Volunteers were examined three times, twice with 0.2 mmol/kg bw gadobutrol using two different flip angles and once with 0.2 mmol/kg bw Gd-DTPA. All contrast injections were performed at a rate of 5 mL/second. Image analysis included signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurements in lung arteries and veins, as well as a subjective analysis of image quality. RESULTS: In patients, significantly higher SNR and CNR were observed with Gd-DTPA compared to both doses of gadobutrol (SNR: 35-42 vs.17-25; CNR 33-39 vs. 16-23; P < or = 0.05). No relevant differences were observed between 0.1 mmol/kg bw and 0.2 mmol/kg bw gadobutrol. In volunteers, gadobutrol and Gd-DTPA achieved similar SNR and CNR. A significantly higher SNR and CNR was observed for gadobutrol-enhanced MRA with an increased flip angle of 40 degrees. Image quality was rated equal for both contrast agents. CONCLUSION: No relevant advantages of 1.0 M gadobutrol over 0.5 M Gd-DTPA were observed for time-resolved pulmonary MRA in this study. Potential explanations are T2/T2*-effects caused by the high intravascular concentration when using high injection rates.

The role of MRI in patients with astrocytoma WHO II treated with fractionated stereotactic radiotherapy.

Aim of this study was to evaluate the role of pre-therapeutic and follow-up MRI in the clinical treatment and outcome in patients with astrocytoma WHO grade II after fractionated stereotactic radiation therapy (FSRT). One hundred thirty-nine patients with histologically proven astrocytoma WHO grade II were treated with FSRT and retrospectively evaluated. All patients had follow-up MRI studies (Gd-DTPA-enhanced T1- and T2-weighted MR images). Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method. Multivariate analysis was performed on five potential MRI related prognosticators. Median follow-up was 3.8 years. Positive contrast enhancement (CM+) prior to FSRT proved to be a significant prognosticator for PFS and OS (p<0.01). Pre-therapeutic oedema on T2-weighted images and multifocality of contrast medium (CM) enhancement did not prove to be significant prognosticators. Also, diameter and volume of CM enhancement showed no significance on clinical outcome. Negative contrast enhancing (CM-) patients developing a de novo CM enhancement during follow-up showed a significantly worse clinical outcome compared with generally CM- patients (p<0.05). Pre-therapeutic CM enhancement and the development of CM-enhancing areas during follow-up are negative prognosticators for PFS and OS. They must be interpreted as signs of secondary malignity.

High-resolution three-dimensional MR angiography of rodent tumors: morphologic characterization of intratumoral vasculature.

PURPOSE: To evaluate high-resolution three-dimensional MR angiography (MRA) for the visualization and morphologic characterization of intratumoral vasculature. MATERIALS AND METHODS: Two subcutaneous rodent tumor models (human skin carcinoma HaCaT-ras-A-5RT3 grown in nude mice and rat prostate carcinoma R3327-AT1 grown in Copenhagen rats) were examined with a clinical 1.5 T MR-system. For MRA a dedicated high-resolution three-dimensional gradient echo pulse sequence with a voxel size of 166 x 206 x 320 microm(3) was performed after injection of Gadomer-17. The image analysis included a correlation of intratumoral vessels with histology. Signal intensity measurements were performed in the vena cava, the tumor underlying muscle, and in various regions of the tumor. Signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were calculated from this measurement. RESULTS: High-resolution MRA allowed a clear distinction of intratumoral blood vessels. The mouse tumor model tended to be strongly vascularized with several intratumoral blood vessels clearly displayed by MRA. When correlated with histology, these intratumoral blood vessels had a size in the range of 300 to 400 microm. In contrast, rat tumors had only sparse capillary intratumoral blood vessels that could only be demonstrated by histology. In both tumor models, dilated blood vessels were observed in the subcutaneous tissue near the tumor. In general, areas with a strong contrast enhancement correlated with viable, well vascularized tumor regions, whereas non-enhancing tumor areas correlated with tumor necrosis or hypoxic areas. CONCLUSION: High-resolution three-dimensional MRA allows the visualization of intratumoral vasculature in rodent models. With minimal hardware and software modifications, high-resolution MRA could be performed on a clinical 1.5 T MRI scanner. Morphologic characterization of intratumoral blood vessels could add important insights into the process of tumor angiogenesis.