Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma.

This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a non-invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE-MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE-MRI of the lumbar spine. Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0·001, hazard ratio (HR) 2·42, multivariate P = 0·02, HR 2·7) and exchange rate constant kep (univariate P = 0·03, HR 1·92, multivariate P = 0·46, HR 1·5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut-off point of 0·89 arbitrary units had a 2-year progression rate into symptomatic disease of 80%. In conclusion, DCE-MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS.

Prognostic significance of increased bone marrow microcirculation in newly diagnosed multiple myeloma: results of a prospective DCE-MRI study.

OBJECTIVES: Aim of this prospective study was to investigate prognostic significance of increased bone marrow microcirculation as detected by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for survival and local complications in patients with multiple myeloma (MM). METHODS: We performed DCE-MRI of the lumbar spine in 131 patients with newly diagnosed MM and analysed data according to the Brix model to acquire amplitude A and exchange rate constant kep. In 61 patients a second MRI performed after therapy was evaluated to assess changes in vertebral height and identify vertebral fractures. RESULTS: Correlation analysis revealed significant positive association between beta2-microglobulin as well as immunoparesis with DCE-MRI parameters A and kep. Additionally, A was negatively correlated with haemoglobin levels and kep was positively correlated with LDH levels. Higher baseline kep values were associated with decreased vertebral height in a second MRI (P = 0.007) and A values were associated with new vertebral fractures in the lower lumbar spine (P = 0.03 for L4). Pre-existing lytic bone lesions or remission after therapy had no impact on the occurrence of vertebral fractures. Multivariate analysis revealed that amplitude A is an independent adverse risk factor for overall survival. CONCLUSION: DCE-MRI is a non-invasive tool with significance for systemic prognosis and vertebral complications. KEY POINTS: • Qualitative parameters from DCE-MRI are correlated with established factors of disease activity • Increased marrow microcirculation might be a risk factor for loss of vertebral height and fractures • Amplitude A is an independent predictor for shortened overall survival.

Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy.

INTRODUCTION: Since the prostate-specific membrane antigen (PSMA) is frequently over-expressed in prostate cancer (PCa) several PSMA-targeting molecules are under development to detect and treat metastatic castration resistant prostate cancer (mCRPC). We investigated the tissue kinetics of a small molecule inhibitor of PSMA ((S)-2-(3-((S)-1-carboxy-5-(3-(4-[(124)I]iodophenyl)ureido)pentyl)ureido)pentanedioicacid; MIP-1095) using PET/CT to estimate radiation dosimetry for the potential therapeutic use of (131)I-MIP-1095 in men with mCRPC. We also report preliminary safety and efficacy of the first 28 consecutive patients treated under a compassionate-use protocol with a single cycle of (131)I-MIP-1095. METHODS: Sixteen patients with known prostate cancer underwent PET/CT imaging after i.v. administration of (124)I-MIP-1095 (mean activity: 67.4 MBq). Each patient was scanned using PET/CT up to five times at 1, 4, 24, 48 and 72 h post injection. Volumes of interest were defined for tumor lesions and normal organs at each time point followed by dose calculations using the OLINDA/EXM software. Twenty-eight men with mCRPC were treated with a single cycle of (131)I-MIP-1095 (mean activity: 4.8 GBq, range 2 to 7.2 GBq) and followed for safety and efficacy. Baseline and follow up examinations included a complete blood count, liver and kidney function tests, and measurement of serum PSA. RESULTS: I-124-MIP-1095 PET/CT images showed excellent tumor uptake and moderate uptake in liver, proximal intestine and within a few hours post-injection also in the kidneys. High uptake values were observed only in salivary and lacrimal glands. Dosimetry estimates for I-131-MIP-1095 revealed that the highest absorbed doses were delivered to the salivary glands (3.8 mSv/MBq, liver (1.7 mSv/MBq) and kidneys (1.4 mSv/MBq). The absorbed dose calculated for the red marrow was 0.37 mSv/MBq. PSA values decreased by >50 % in 60.7 % of the men treated. Of men with bone pain, 84.6 % showed complete or moderate reduction in pain. Hematological toxicities were mild. Of men treated, 25 % had a transient slight to moderate dry mouth. No adverse effects on renal function were observed. CONCLUSION: Based on the biodistribution and dose calculations of the PSMA-targeted small molecule (124)I-MIP-1095 therapy with the authentic analog (131)I-MIP-1095 enables a targeted tumor therapy with unprecedented doses delivered to the tumor lesions. Involved lymph node and bone metastases were exposed to estimated absorbed doses upwards of 300 Gy.

Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer.

PURPOSE: Positron emission tomography (PET) with choline tracers has found widespread use for the diagnosis of prostate cancer (PC). However, choline metabolism is not increased in a considerable number of cases, whereas prostate-specific membrane antigen (PSMA) is overexpressed in most PCs. Therefore, a (68)Ga-labelled PSMA ligand could be superior to choline tracers by obtaining a high contrast. The aim of this study was to compare such a novel tracer with standard choline-based PET/CT. METHODS: Thirty-seven patients with biochemical relapse of PC [mean prostate-specific antigen (PSA) 11.1 ± 24.1 ng/ml, range 0.01-116] were retrospectively analysed after (18)F-fluoromethylcholine and (68)Ga-PSMA PET/CT within a time window of 30 days. Radiotracer uptake that was visually considered as PC was semi-quantitatively analysed by measuring the maximum standardized uptake values (SUVmax) of the scans acquired 1 h after injection of (68)Ga-PSMA complex solution (median 132 MBq, range 59-263 MBq) and (18)F-fluoromethylcholine (median 237 MBq, range 114-374 MBq), respectively. In addition, tumour to background ratios were calculated. RESULTS: A total of 78 lesions characteristic for PC were detected in 32 patients using (68)Ga-PSMA PET/CT and 56 lesions were detected in 26 patients using choline PET/CT. The higher detection rate in (68)Ga-PSMA PET/CT was statistically significant (p=0.04). In five patients no lesion was found with both methods. All lesions detected by (18)F-fluoromethylcholine PET/CT were also seen by (68)Ga-PSMA PET/CT. In (68)Ga-PSMA PET/CT SUVmax was clearly (>10 %) higher in 62 of 78 lesions (79.1 %) and the tumour to background ratio was clearly (>10 %) higher in 74 of 78 lesions (94.9 %) when compared to (18)F-fluoromethylcholine PET/CT. CONCLUSION: (68)Ga-PSMA PET/CT can detect lesions characteristic for PC with improved contrast when compared to standard (18)F-fluoromethylcholine PET/CT, especially at low PSA levels.

Comparison of gadobenate dimeglumine-enhanced breast MRI and gadopentetate dimeglumine-enhanced breast MRI with mammography and ultrasound for the detection of breast cancer.

PURPOSE: To compare gadobenate dimeglumine-enhanced magnetic resonance imaging (MRI) with gadopentetate dimeglumine-enhanced MRI, mammography, and ultrasound for breast cancer detection across different malignant lesion types and across different densities of breast tissue. MATERIALS AND METHODS: In all, 153 women with Breast Imaging Reporting and Data System (BI-RADS) 3­5 findings on mammography and/or ultrasound underwent identical breast MRI exams at 1.5T with gadobenate dimeglumine and gadopentetate dimeglumine. Images were evaluated by three independent blinded radiologists. Mammography, ultrasound, and combined mammography and/or ultrasound findings were available for 108, 109, and 131 women. Imaging findings were matched with histology data by a fourth, independent, blinded radiologist. Malignant lesion detection rates and diagnostic performance were compared. RESULTS: In all, 120, 120, and 140 confirmed malignant lesions were present in patients undergoing MRI+mammography, MRI+ultrasound, and MRI+mammography and/or ultrasound, respectively. Significantly greater cancer detection rates were noted by all three readers for comparisons of gadobenate dimeglumine-enhanced MRI with mammography (Δ15.8­17.5%; P < 0.0001), ultrasound (Δ18.3­20.0%; P < 0.0001), and mammography and/or ultrasound (Δ8.6­10.7%; P ≤ 0.0105) but not for comparisons of gadopentetate dimeglumine-enhanced MRI with conventional techniques (P > 0.05). The false-positive detection rates were lower on gadobenate dimeglumine-enhanced MRI than on conventional imaging (4.0­5.5% vs. 11.1% at mammography; 6.3­8.4% vs. 15.5% at ultrasound). Significantly improved cancer detection on MRI was noted in heterogeneously dense breast (91.2­97.3% on gadobenate dimeglumine-enhanced MRI vs. 77.2­84.9% on gadopentetate dimeglumine-enhanced MRI vs. 71.9-84.9% with conventional techniques) and for invasive cancers (93.2­96.2% for invasive ductal carcinoma [IDC] on gadobenate dimeglumine-enhanced MRI vs. 79.7­88.5% on gadopentetate dimeglumine-enhanced MRI vs. 77.0­84.4% with conventional techniques). Overall diagnostic performance for the detection of cancer was superior on gadobenate dimeglumine-enhanced MRI than on conventional imaging or gadopentetate dimeglumine-enhanced MRI. CONCLUSION: Gadobenate dimeglumine-enhanced MRI significantly improves cancer detection compared to gadopentetate dimeglumine-enhanced MRI, mammography, and ultrasound in a selected group of patients undergoing breast MRI for preoperative staging or because of inconclusive findings at conventional imaging.

Reproducibility of 3D 1H MR spectroscopic imaging of the prostate at 1.5T.

PURPOSE: To determine the reproducibility of 3D proton magnetic resonance spectroscopic imaging ((1)H-MRSI) of the human prostate in a multicenter setting at 1.5T. MATERIALS AND METHODS: Fourteen subjects were measured twice with 3D point-resolved spectroscopy (PRESS) (1)H-MRSI using an endorectal coil. MRSI voxels were selected in the peripheral zone and combined central gland at the same location in the prostate in both measurements. Voxels with approved spectral quality were included to calculate Bland-Altman parameters for reproducibility from the choline plus creatine to citrate ratio (CC/C). The repeated spectroscopic data were also evaluated with a standardized clinical scoring system. RESULTS: A total of 74 voxels were included for reproducibility analysis. The complete range of biologically interesting CC/C ratios was covered. The overall within-voxel standard deviation (SD) of the CC/C ratio of the repeated measurements was 0.13. This value is equal to the between-subject SD of noncancer prostate tissue. In >90% of the voxels the standardized clinical score did not differ relevantly between the measurements. CONCLUSION: Repeated measurements of in vivo 3D (1)H-MRSI of the complete prostate at 1.5T produce equal and quantitative results. The reproducibility of the technique is high enough to provide it as a reliable tool in assessing tumor presence in the prostate.

Multicenter, double-blind, randomized, intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for Breast MR imaging (DETECT Trial).

PURPOSE: To intraindividually compare 0.1 mmol/kg doses of gadobenate dimeglumine and gadopentetate dimeglumine for contrast material-enhanced breast magnetic resonance (MR) imaging by using a prospective, multicenter double-blind, randomized protocol. MATERIALS AND METHODS: Institutional review board approval and patient informed consent were obtained. One hundred sixty-two women (mean age, 52.8 years ± 12.3 [standard deviation]) enrolled at 17 sites in Europe and China between July 2007 and May 2009 underwent at least one breast MR imaging examination at 1.5 T by using three-dimensional spoiled gradient-echo sequences. Of these, 151 women received both contrast agents in randomized order in otherwise identical examinations separated by more than 2 but less than 7 days. Images, acquired at 2-minute or shorter intervals after contrast agent injection, were evaluated independently by three blinded radiologists unaffiliated with enrollment centers. Histopathologic confirmation was available for all malignant lesions (n = 144), while benign lesions were confirmed either by using histopathologic examination (n = 52) or by at least 12-month diagnostic follow-up (n = 20) with mammography and/or ultrasonography. Determinations of malignant lesion detection rates and diagnostic performance (sensitivity, specificity, accuracy, positive predictive value [PPV], and negative predictive value [NPV]) were performed and compared (McNemar and Wald tests). A full safety assessment was performed. RESULTS: Significant superiority for gadobenate dimeglumine was noted by readers 1, 2, and 3 for malignant lesion detection rate (91.7%, 93.1%, 94.4% vs 79.9%, 80.6%, 83.3%, respectively; P ≤ .0003). Readers 1, 2, and 3 reported significantly superior diagnostic performance (sensitivity, specificity, and accuracy) for breast cancer detection with gadobenate dimeglumine (91.1%, 94.5%, 95.2% vs 81.2%, 82.6%, 84.6%; 99.0%, 98.2%, 96.9% vs 97.8%, 96.9%, 93.8%; 98.2%, 97.8%, 96.7% vs 96.1%, 95.4%, 92.8%, respectively; P ≤ .0094) and significantly superior PPV (91.1%, 85.2%, 77.2% vs 80.7%, 75.5%, 60.9%, respectively; P ≤ .0002) and NPV (99.0%, 99.4%, 99.4% vs 97.8%, 98.0%, 98.1%, respectively; P ≤ .0003). No safety concerns were noted with either agent. CONCLUSION: Gadobenate dimeglumine is superior to gadopentetate dimeglumine for breast cancer diagnosis. © RSNA, 2010 Clinical trial registration no. NCT00486473 (http://www.clinicaltrials.gov/). SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100968/-/DC1.

Respiratory-induced prostate motion: characterization and quantification in dynamic MRI.

BACKGROUND AND PURPOSE: To investigate prostate movement during deep breathing and contraction of abdominal musculature by means of dynamic MRI and analyze implications for image-guided radiotherapy of prostate cancer. PATIENTS AND METHODS: A total of 43 patients and 8 healthy volunteers were examined with MRI. Images during deep respiration and during contraction of abdominal musculature (via a coughing maneuver) were obtained with dynamic two-dimensional (2D) balanced SSFP; 3 frames/s were obtained over an acquisition time of 15 s. Images were acquired in sagittal orientation to evaluate motion along both the craniocaudal (cc)-axis and anteroposterior (ap)-axis. Prostate motion was quantified semi-automatically using dedicated software tools. RESULTS: Respiratory induced mean cc-axis displacement of the prostate was 2.7 ± 1.9 (SD) mm (range, 0.5-10.6 mm) and mean ap-axis displacement 1.8 ± 1.0 (SD) mm (range, 0.3-10 mm). In 69% of the subjects, breathing-related prostate movements were found to be negligible (< 3 mm). The prostate displacement for abdominal contraction was significantly higher: mean cc-axis displacement was max. 8.4 ± 6.7 (SD) mm (range, 0.6-27 mm); mean anteroposterior movement was 8.3 ± 7.7 (SD) mm (range, 0.7-26 mm). CONCLUSION: Dynamic MRI is an excellent tool for noninvasive real-time imaging of prostate movement. Further investigations regarding possible applications in image-guided radiotherapy, e.g., for individualized planning and in integrated linac/MRI systems, are warranted.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging of bone marrow in healthy individuals.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) displays microcirculation and permeability by application of contrast-media and diffusion-weighted imaging (DWI) is a tool for quantification of cellularity in the investigated area. Recently published examples cover breast cancer, CNS tumors, head and neck cancer, gastrointestinal cancer, prostate cancer as well as hematologic malignancies. PURPOSE: To investigated the influence of age, sex, and localization of the investigated region on findings of DCE-MRI and DWI. MATERIAL AND METHODS: DCE-MRI-parameters amplitude A and exchange rate constant kep as well as the DWI-parameter ADC of the bone marrow of the lumbar vertebral column of 30 healthy individuals covering the typical range of age of tumor patients were evaluated. ADC was calculated using b=0 and a maximal b value of either 400 or 750 s/mm(2). RESULTS: Amplitude A of DCE-MRI decreased with age (P = 0.01) and amplitude A, exchange rate constant kep as well as ADC based on b = 400 s/mm(2) and b = 750 s/mm(2,) respectively, decreased significantly from the first to the fifth lumbar vertebra with P = 0.02, P = 0.05, P = 0.003, and P = 0.002, respectively. CONCLUSION: Quantitative parameters of functional imaging techniques in bone marrow are influenced by the age of the examined individual and the anatomical location of the investigated region.

Anterior cruciate ligament reconstruction using patellar tendon versus hamstring tendon: a prospective comparative study with 9-year follow-up.

PURPOSE: To analyze the long-term evaluation of clinical, functional, and magnetic resonance imaging (MRI) results after implant-free press-fit anterior cruciate ligament (ACL) reconstruction with bone-patella tendon (BPT) versus quadrupled hamstring tendon (HT) grafts. METHODS: Sixty-two ACL-insufficient patients were included in a prospective, randomized study (31 BPT and 31 HT). Both surgical procedures were performed without any implants by a press-fit technique by the senior author. The femoral tunnel was drilled through the anteromedial portal for anatomic placement. At 8.8 years after reconstruction, 53 patients (28 BPT and 25 HT) were examined by different clinical and functional tests. Bilateral MRI scans were performed and interpreted by an independent radiologist. RESULTS: On follow-up, the score on the International Knee Documentation Committee evaluation form was significantly better in the HT group. The clinical examination including range of motion, KT-1000 test (MEDmetric, San Diego, CA), and pivot-shift test showed no significant differences. On isokinetic testing, the mean quadriceps strength was close to normal (96%) in both groups, but the hamstring strength was lower in the HT group (100.3%/95.1%). Kneeling (1.5/1.1, P = .002), knee walking (1.72/1.14, P = .002), and single-leg hop test (95.8%/99.1%, P = .057) were better in the HT group. The MRI findings about the mean degree of cartilage lesion (International Cartilage Repair Society protocol) of the operated (2.1/2.1) and nonoperated (1.4/1.8) knee showed no significant differences. No significant difference was found in the grade of medial or lateral meniscal lesion or the number of patients having meniscal lesions when the operated and nonoperated knees were compared. Tunnel measurements, Caton-Deschamps Index, and the sagittal ACL angle were similar. CONCLUSIONS: The implant-free press-fit technique for anterior cruciate ligament reconstruction by use of bone-patellar tendon and hamstring grafts with anatomic graft placement is an innovative technique to preserve the cartilage and meniscal status without significant differences between the operated and nonoperated knees in the long term. Significantly less anterior knee pain was noted in the hamstring group, when testing for kneeling and knee walking. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Comparison of peripheral zone and central gland volume in patients undergoing intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: The shrinking effect of androgen deprivation therapy (ADT) and radiotherapy (RT) on prostate gland volume is a known clinical finding. Until now, it is not known which part of the prostate shrinks more. We examined patients with and without ADT undergoing intensity-modulated RT (IMRT) and performed 3-dimensional measurements of the peripheral zone (PZ) and central gland (CG) with magnetic resonance imaging (MRI). METHODS AND MATERIALS: Prostate gland volumes of PZ and CG between planning MRI and first available follow-up MRI were retrospectively determined in 44 patients with localized prostate carcinoma. A total of 24 patients had ADT with a median time interval of 5 months (range, 1.5-24 months). Median time interval between both MRI time points was 132 days (range, 104-224 days). Two observers performed PZ and CG delineation in consensus using planimetry. Volume changes over time were determined and compared. RESULTS: Patients who had ADT showed smaller prostate volume in the first MRI (mean [SD], 32 [16.7] mL), which was still present after IMRT (28.1 [16.7] mL). Patients who had no ADT started with 44.6 (16.9) mL and showed 37.5 (13.9) mL after IMRT. Shrinking effect in PZ was significantly larger than in CG for all patients (-18.3% vs -6.3%, P < 0.05). CONCLUSIONS: Because, typically, most tumors are located in PZ and this area also shows the largest shrinkage effect after IMRT, this should be taken into account for planning purposes. Notably, there are only minor differences in the relative shrinking effects between patients with and without ADT, although they start with different volumes.

Detection Rate of 18F-Fluorethylcholine-PET/CT in relation to PSA Value in PCA Patients Referred with Biochemical Relapse.

Attempts to predict the likelihood of positive morphological imaging related with PSA value in patients referred with biochemical recurrence were the focus of many studies. Using nuclear medicine modalities, numerous studies likewise had been performed for the same purpose, however mostly using C-11-labeled choline. For this purpose, we selected 193 prostate cancer patients from our database between 2006 and 2010. They had been referred to our department to undergo 18F-fluorethylcholine (FECH)-PET/CT due to biochemical recurrence after potentially curative procedures. As a result, in 84 out of 193 patients, 18F-FECH-PET demonstrated positive findings with an overall detection rate of 44%. Statistically, there was a significant difference in PSA values in positive findings vs. negative findings (p < 0.001), and there was a linear correlation between the detection rate and PSA value (r = 0.91). Moreover, there was a relation between initial therapy and recurrence type. So, the local relapse was the most frequent recurrence (>70%) after radiation therapy alone. By contrast, patients after radical prostatectomy followed by salvage radiotherapy showed a low likelihood of local recurrence. In conclusion, PSA value was confirmed to have a determinant role in 18F-FECH-PET outcome. Moreover, there was a link between recurrence type and initial therapy, which-if prospectively confirmed-may play a guiding role in selecting the appropriate diagnostic methods.

Multiple myeloma and monoclonal gammopathy of undetermined significance: importance of whole-body versus spinal MR imaging.

PURPOSE: To examine if standard magnetic resonance (MR) imaging of the axial skeleton is sufficient for evaluation of patients with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) or if whole-body MR is necessary. MATERIALS AND METHODS: A total of 100 untreated patients with MGUS (n = 27) or any stages of MM (n = 73) were examined with whole-body MR imaging and MR imaging of the axial skeleton. The study was approved by the institutional ethics committee, and written informed consent was given. Spinal pattern ("no diffuse involvement" or "diffuse involvement" as assessed from the signal intensity of the spinal bone marrow), serum parameters, and stage of disease were correlated with the probability of detecting extra-axial lesions with and without destruction of cortical bone by using a multiple logistic regression model. RESULTS: Of 100 patients, 39 had lesions in the axial skeleton and 37 had lesions in the extra-axial skeleton. Of the latter group, nine patients had no axial lesions and 13 patients had lesions that violated cortical bone, which implied an increased fracture risk. Because of the extraaxial location, lesions in these patients could be diagnosed with whole-body MR only. In addition, no single or combination of clinical factors observed (stage of disease, serum parameters, and spinal pattern) allowed investigators to identify patients with a significantly increased probability of having extra-axial lesions or lesions violating cortical bone. CONCLUSION: Whole-body MR imaging has potential for use in the initial work-up of patients with MGUS or MM, since almost one-half of all observed lesions would have been missed by using spinal MR imaging only and clinical parameters could not exclude the presence of extra-axial lesions.

Changes of prostate gland volume with and without androgen deprivation after intensity modulated radiotherapy - A follow-up study.

BACKGROUND AND PURPOSE: The shrinking effect of androgen deprivation therapy (ADT) on prostate volume is a known finding, but data on volume changes during radiotherapy are inconsistent. We examined patients with and without ADT undergoing intensity modulated radiotherapy (IMRT) and performed follow-up examinations to study volume changes before and after radiotherapy. METHODS AND MATERIALS: Prostate volumes between planning magnetic resonance imaging (MRI) and last available follow-up MRI were retrospectively determined in 39 patients. Median time interval between first and last MRI was 233days (range 126-813). Two observers performed volume measurements in consensus and were blind to the timing of MRI. Volume changes over MRI were determined using the ellipsoid formula. Data of patients with and without ADT were compared by a linear mixed model. RESULTS: Of 39 patients, 22 had ADT with a median duration of 5months (range 1-24). ADT patients showed lower prostate volume throughout the study period (-28% to 38%). Although individual shrinking effect was highly variable, patients treated with IMRT but without ADT showed a significantly larger volume reduction (26.1%) than patients with ADT (12.9%, p<0.05). CONCLUSIONS: Patients undergoing IMRT show definite prostate shrinkage. The rate is slowed down after 6months in both groups, whereas the volume reduction is significantly larger in patients without ADT. Nevertheless there is no adding effect of ADT+IMRT vs. IMRT alone.

Intraindividual comparison between gadopentetate dimeglumine and gadobutrol for magnetic resonance perfusion in normal brain and intracranial tumors at 3 Tesla.

BACKGROUND: In vitro studies have shown that the 3-Tesla (T) magnetic resonance (MR) characteristics of high- and standard-molar gadolinium-based contrast agents differ. Such differences may indicate that high-molar (1.0 M) agents offer advantages for perfusion-weighted imaging (PWI) at 3T, as has been previously reported at 1.5 T. PURPOSE: To investigate possible intraindividual differences of high- versus low-molar contrast agents on PWI at 3T in patients with intracranial space-occupying lesions. MATERIAL AND METHODS: Six patients with intraaxial and five patients with extraaxial tumors underwent two MR examinations at 3T, separated by at least 48 hours. On each occasion, an exogenous contrast-based, T2*-weighted, gradient-recalled echo-planar imaging (EPI) technique was used to determine the intracranial perfusion characteristics using one of two intravenous contrast agents: either 5 ml of 1.0 M gadobutrol or 10 ml of 0.5 M gadopentetate dimeglumine. The primary PWI outcome measure was region-of-interest maximal signal change (C(max)). RESULTS: The difference in C(max) for gray and white matter (Delta C(max)) was significantly higher for gadobutrol compared to gadopentetate dimeglumine (P<0.01). The ratio of C(max) between gray and white matter (rC(max) = C(maxGray)/C(maxWhite)) was also significantly higher (median 24.6%, range 13.7-36.5%) for gadobutrol (P<0.01). The ratio of C(max) between the whole tumor and whole normal side hemisphere was higher in five out of the six intraaxial tumor cases. A significantly higher ratio (Delta C(max)/C(max)) in the difference between C(max) of gray and white matter (from hemisphere without brain lesion) compared to C(max) for the hemisphere containing the neoplasm (hemisphere with brain lesion) was demonstrated for gadobutrol in intraaxial tumors (P<0.05). CONCLUSION: Higher-concentration 1.0 M gadobutrol can offer advantages over standard 0.5 M gadopentetate dimeglumine, particularly with respect to delineation between gray and white matter and for the demarcation of highly vascularized tumor tissue on brain PWI performed at 3T.

Gain of 1q21 and distinct adverse cytogenetic abnormalities correlate with increased microcirculation in multiple myeloma.

To identify genetic mechanisms controlling bone marrow microcirculation and angiogenesis in patients with plasma cell disease we simultaneously performed bone marrow dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and cytogenetics (iFISH) on CD138 purified plasma cells of MGUS (n=31) and untreated multiple myeloma (MM) (n = 87) patients. The adverse cytogenetic abnormalities gain of 1q21, deletion 17p13 and deletion 13q14 significantly correlated with at least one DCE-MRI finding (aberrant "focal" microcirculation pattern, increase in median microcirculation parameter Amplitude A or exchange rate constant kep). We conclude that gain of 1q21, deletion 13q14 and deletion 17p13 trigger the angiogenic cascade in MM. Our findings will have important implications for the design, analysis and stratification for clinical studies of patients with MM in particular if compounds with antiangiogenic activity are used.

Pharmacokinetic analysis of malignant pleural mesothelioma-initial results of tumor microcirculation and its correlation to microvessel density (CD-34).

RATIONALE AND OBJECTIVES: Malignant mesothelioma (MM) of the pleura is an aggressive and often fatal neoplasm. Because MM frequently demonstrates marked angiogenesis, it may be responsive to antiangiogenic therapy, but effective methods for selecting and monitoring of patients are further needed. We employed dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and quantitative immunohistochemistry (IHC) to characterize the microvascularity of MM using both a physiologic and ultrastructural method. MATERIALS AND METHODS: Nineteen patients diagnosed with MM were enrolled and DCE-MRI was performed before antiangiogenic treatment. For each patient, tumor regions were characterized by their DCE-MRI-derived pharmacokinetic parameters (Amp, k(ep), k(el)), which were also compared to those of normal tissue (aorta, liver, spleen, and muscle). In addition, quantitative IHC of representative samples was performed with CD-34 staining to compare the calculated microvessel density (MVD) results with DCE-MRI results. RESULTS: MM demonstrated markedly abnormal pharmacokinetic properties compared with normal tissues. Among the parameters tested, Amp was significantly different in MM (P < or = .001) compared to normal organs. Despite the observation that the MVD of mesotheliomas in this series was high compared to other tumors, DCE-MRI pharmacokinetic parameters had a moderately positive correlation with MVD (r = 0.5). CONCLUSIONS: DCE-MRI and IHC can be used in patients with MM to visualize tumor microvascularity and to characterize tumor heterogeneity. DCE-MRI and IHC results positively correlated, though moderately, but these two methods present as essential tumor biomarkers. This multimodal characterization may be useful in selecting possible tumor subtypes that would benefit from antiangiogenic therapy.

Dynamic contrast-enhanced MRI of malignant pleural mesothelioma: a feasibility study of noninvasive assessment, therapeutic follow-up, and possible predictor of improved outcome.

STUDY OBJECTIVE: Dynamic contrast-enhanced MRI (DCE-MRI) followed by pharmacokinetic analysis has been successfully used in a variety of solid tumors. The aims of this study were to evaluate the feasibility of DCE-MRI in malignant pleural mesothelioma (MPM), to differentiate benign from pathologic tissue and compare pharmacokinetic with clinical parameters and survival in order to map out its microcirculation; and to compare pharmacokinetic with clinical parameter and survival in order to improve our understanding of the in vivo biology of this malignancy. METHODS: Nineteen patients with a diagnosis of MPM who were scheduled to receive chemotherapy with gemcitabine were enrolled in the study. DCE-MRI was performed before treatment (n = 19) and after the third cycle (n = 12) and sixth cycle (n = 7) of chemotherapy. An established pharmacokinetic two-compartment model was used to analyze DCE-MRI. Tumor regions were characterized by the pharmacokinetic parameters amplitude (Amp), redistribution rate constant (kep), and elimination rate constant (kel). Kinetic parameters of tumor tissue and normal tissue were compared using the Student t test. Patients were classified as clinical responders or nonresponders according to clinical outcome, and these groups were compared with the pharmacokinetic parameters derived from DCE-MRI. RESULTS: Normal and tumor tissue could be distinguished by the pharmacokinetic parameters Amp and kel (p

Qualitative and quantitative image analysis of CT and MR imaging in patients with neuroendocrine liver metastases in comparison to (68)Ga-DOTATOC PET.

PURPOSE: To compare lesion conspicuity in patients with liver metastases arising from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using MRI, PET and CT. MATERIALS AND METHODS: 16 patients with GEP-NETs were evaluated using non-contrast MRI, contrast-enhanced (CE) MRI using Gd-EOB-DTPA and CE-(68)Ga-DOTATOC PET. Quantitative analyses were performed by two blinded readers using ROI-analyses quantifying contrast ratios (CR) between normal liver-tissue and GEP-NET-metastases. Qualitative analyses were performed evaluating primary visibility and spatial detectability of all lesions. RESULTS: 103 of the same liver metastases were detected on all modalities. Qualitatively, lesion conspicuity was superior on CE-MRI imaging compared to non-contrast MR-sequences (T2, DWI, fl2D, fl3D), as well as arterial- and portal-venous phase CT. Concerning detectability of lesions, CE-MRI was superior to all other modalities. The quantitative ROI-analysis demonstrated improved CR for DWI compared to all other non-contrast MR-sequences (p<0.001). CE-MRI presented with higher CR-values compared to CE-(68)Ga-DOTATOC PET/CT (p<0.001). CONCLUSIONS: Anatomic imaging using non contrast MRI with fl2D-and fl3D-sequences in combination with the molecular imaging modality (68)Ga-DOTATOC PET is optimal for the assessment of liver lesions in GEP-NET-patients. Even though CE-MRI was superior to non-contrast MRI, non-contrast MRI is sufficient to detect and quantify liver metastases in daily routine, especially in combination with DW-Imaging.