Can high-spatial resolution T2-weighted endorectal MRI rule out clinically significant prostate cancer?

PURPOSE: To evaluate whether clinically significant prostate cancer (PCa) can be ruled out by high-spatial resolution T2-weighted endorectal MRI (eMRI) in a cohort of patients with biopsy-proven PCa. PATIENTS AND METHODS: A retrospective analysis was carried out for consecutive patients who underwent 1.5 Tesla eMRI for local staging before open radical prostatectomy. The cohort was dichotomized into patients with apparent or inapparent tumour on eMRI. The results were compared with final histopathology, and an analysis for presence of clinically significance PCa was performed. RESULTS: A total of 385 patients were included in the study; in 85 patients (22 %), no apparent lesion suspicious for PCa was detected on eMRI, still final pathology revealed clinically significant PCa in 61 of these patients (72 %). In contrast, 256 (85 %) of the 300 patients with apparent tumour in eMRI harboured clinically significant PCa. eMRI could not differentiate clinically significant from insignificant PCa in neither of the groups (p > 0.6). CONCLUSIONS: Presence of clinically significant cancer cannot be excluded by high-resolution 1.5 Tesla T2-weighted eMRI. The results of the study suggest that the role of T2-weighted eMRI for selecting patients suitable for AS is limited.

Accuracy of preoperative endorectal MRI in predicting extracapsular extension and influence on neurovascular bundle sparing in radical prostatectomy.

PURPOSE: To evaluate the accuracy of presurgical endorectal MRI (eMRI) for local staging before radical prostatectomy (RP) and its influence on neurovascular bundle (NVB) resection during radical prostatectomy. PATIENTS AND METHODS: A total of 385 patients with histologically proven prostate cancer (PCa) have been included in this retrospective study between 2004 and 2008. All patients underwent preoperative eMRI at 1.5 T before open RP. Staging results by eMRI were compared with the histopathological findings. The presence of positive surgical margins and extent of nerve-sparing procedure were evaluated. Subgroup analysis of low-risk group and intermediate to high-risk group based on D'Amico criteria was conducted. RESULTS: In 294 (76.4%) patients, pathological stage was correctly predicted, 69 patients (17.9%) were understaged and 22 (5.7%) overstaged. Overall sensitivity, specificity, negative and positive predictive value for predicting extracapsular extension (ECE) were 41.5, 91.8, 78.0 and 69.0%, respectively. One hundred and fifty-two (48.4%) of the patients classified as stage cT2 by eMRI underwent bilateral NVB sparing, whereas 14 (19.7%) patients with reported ECE underwent bilateral NVB sparing (P < 0.01). Overall positive surgical margin rate was 14.8%. Sensitivity of predicting ECE and positive predictive value were lower in the low-risk group than in the intermediate and high-risk group. CONCLUSIONS: eMRI is effective in predicting extracapsular extension in an intermediate to high-risk group. Preoperative eMRI in patients with low-risk criteria is not recommended as a routine assessment modality. eMRI findings did appear to influence surgical strategy as patients with imaging findings suggesting >cT2 disease were less likely to undergo NVB sparing.

Multiphase contrast-enhanced CT with highly concentrated contrast agent can be used for PET attenuation correction in integrated PET/CT imaging.

PURPOSE: State-of-the-art positron emission tomography/computed tomography (PET/CT) systems incorporate multislice CT technology, thus facilitating the acquisition of multiphase, contrast-enhanced CT data as part of integrated PET/CT imaging protocols. We assess the influence of a highly concentrated iodinated contrast medium (CM) on quantification and image quality following CT-based attenuation correction (CT-AC) in PET/CT. METHODS: Twenty-eight patients with suspected malignant liver lesions were enrolled prospectively. PET/CT was performed 60 min after injection of 400 MBq of (18)F-fluorodeoxyglucose (FDG) and following the biphasic administration of an intravenous CM (400 mg iodine/ml, Iomeron 400). PET images were reconstructed with CT-AC using any of four acquired CT image sets: non-enhanced, pre-contrast (n-PET), arterial phase (art-PET), portal venous phase (pv-PET) and late phase (late-PET). Normal tissue activity and liver lesions were assessed visually and quantitatively on each PET/CT image set. RESULTS: Visual assessment of PET following CT-AC revealed no noticeable difference in image appearance or quality when using any of the four CT data sets for CT-AC. A total of 44 PET-positive liver lesions was identified in 21 of 28 patients. There were no false-negative or false-positive lesions on PET. Mean standardized uptake values (SUV) in 36 evaluable lesions were: 5.5 (n-PET), 5.8 (art-PET), 5.8 (pv-PET) and 5.8 (late-PET), with the highest mean increase in mean SUV of 6%. Mean SUV changes in liver background increased by up to 10% from n-PET to pv-PET. CONCLUSION: Multiphase CT data acquired with the use of highly concentrated CM can be used for qualitative assessment of liver lesions in torso FDG PET/CT. The influence on quantification of FDG uptake is small and negligible for most clinical applications.

Technical performance evaluation of a human brain PET/MRI system.

OBJECTIVES: Technical performance evaluation of a human brain PET/MRI system. METHODS: The magnetic field compatible positron emission tomography (PET) insert is based on avalanche photodiode (APD) arrays coupled with lutetium oxyorthosilicate (LSO) crystals and slip-fits into a slightly modified clinical 3-T MRI system. The mutual interference between the two imaging techniques was minimised by the careful design of the hardware to maintain the quality of the B (0) and B (1) field homogeneity. RESULTS: The signal-to-noise ratio (SNR) and the homogeneity of the MR images were minimally influenced by the presence of the PET. Measurements according to the Function Biomedical Informatics Research Network (FBIRN) protocol proved the combined system's ability to perform functional MRI (fMRI). The performance of the PET insert was evaluated according to the National Electrical Manufacturers Association (NEMA) standard. The noise equivalent count rate (NEC) peaked at 30.7 × 10(3) counts/s at 7.3 kBq/mL. The point source sensitivity was greater than 7 %. The spatial resolution in the centre field of view was less than 3 mm. Patient data sets clearly revealed a noticeably good PET and MR image quality. CONCLUSION: PET and MRI phantom tests and first patient data exhibit the device's potential for simultaneous multiparametric imaging. KEY POINTS: • Combination of PET and MRI is a new emerging imaging technology. • Evaluated brain PET/MRI enables uncompromised imaging performance. • PET/MRI aims to provide multiparametric imaging allowing acquisition of morphology and metabolism.

Volumetric computed tomography (VCT): a new technology for noninvasive, high-resolution monitoring of tumor angiogenesis.

Volumetric computed tomography (VCT) is a technology in which area detectors are used for imaging large volumes of a subject with isotropic imaging resolution. We are experimenting with a prototype VCT scanner that uses flat-panel X-ray detectors and is designed for high-resolution three-dimensional (3D) imaging. Using this technique, we have demonstrated microangiography of xeno-transplanted skin squamous cell carcinomas in nude mice. VCT shows the vessel architecture of tumors and animals with greater detail and plasticity than has previously been achieved, and is superior to contrast-enhanced magnetic resonance (MR) angiography. VCT and MR images correlate well for larger tumor vessels, which are tracked from their origin on 3D reconstructions of VCT images. When compared with histology, small tumor vessels with a diameter as small as 50 microm were clearly visualized. Furthermore, imaging small vessel networks inside the tumor tissue improved discrimination of vital and necrotic regions. Thus, VCT substantially improves imaging of vascularization in tumors and offers a promising tool for preclinical studies of tumor angiogenesis and antiangiogenic therapies.

Topographical sensitivity and specificity of endorectal coil magnetic resonance imaging for prostate cancer detection.

OBJECTIVES: Endorectal coil magnetic resonance imaging (EC-MRI) is useful to evaluate prostate cancer localization. Herein, we evaluate sensitivity and specificity of EC-MRI in different regions of the prostate by comparing the acquired images to whole-mount sections of the prostate after radical prostatectomy. METHODS: 69 patients with localized prostate cancer were included. After virtually dividing the prostate into 12 sectors, results of EC-MRI were compared to corresponding whole-mount sections by contingency analysis. Sensitivity and specificity were calculated for each of the 12 areas as well as for the dorsal and ventral region. RESULTS: Sensitivity right/left was dorsal apex/mid/base 41/41, 60/67 and 73/79%; ventral 33/52, 43/42 and 47/52%. Specificity right/left was dorsal apex/mid/base 92/89, 82/75 and 88/69%; ventral 100/100, 100/92 and 88/83%. Local sensitivity and specificity regarding dorsal versus ventral was 88/100 and 65/87%. CONCLUSIONS: Local sensitivity decreased from basodorsal to apicoventral direction, whereas local specificity increased in the same direction. Therefore, prostate cancers demonstrated by MRI are more prone to be detected in the basodorsal region, whereas less false-positive results are found in the apicoventral region. These variations in topographical specificity and sensitivity need to be considered before radical prostatectomy or MRI-guided biopsy.

Tumor detection by diffusion-weighted MRI and ADC-mapping--initial clinical experiences in comparison to PET-CT.

OBJECTIVE: To evaluate the clinical potential of diffusion-weighted-imaging (DWI) with apparent diffusion coefficient (ADC)-mapping for tumor detection. MATERIALS AND METHODS: A single-shot echo-planar-imaging DWI sequence with fat suppression and ability for navigator-based respiratory triggering was implemented. Nineteen patients (11 melanoma, 4 prostate cancer, 1 non-Hodgkin lymphoma, and 3 lung cancer) were examined by positron emission tomography (PET) with an integrated computed tomography scanner (PET-CT) and DWI. Images at b = 0, 400, and 1000 s/mm2 were acquired and ADC maps were generated. PET examinations were used as a reference for tumor detection. Four hundred twenty-four regions of interest were used for DWI and 73 for PET data evaluation. RESULTS: DWI and ADC maps were of diagnostic quality. Metastases with increased tracer uptake were clearly visualized at b = 1000 s/mm2 with the exception of mediastinal lymph node metastases in cases of lung cancer. ADC mapping did not improve detection rates. CONCLUSIONS: DWI is a feasible clinical technique, improving the assessment of metastatic spread in routine magnetic resonance imaging examinations.

Potential applications of flat-panel volumetric CT in morphologic and functional small animal imaging.

Noninvasive radiologic imaging has recently gained considerable interest in basic and preclinical research for monitoring disease progression and therapeutic efficacy. In this report, we introduce flat-panel volumetric computed tomography (fpVCT) as a powerful new tool for noninvasive imaging of different organ systems in preclinical research. The three-dimensional visualization that is achieved by isotropic high-resolution datasets is illustrated for the skeleton, chest, abdominal organs, and brain of mice. The high image quality of chest scans enables the visualization of small lung nodules in an orthotopic lung cancer model and the reliable imaging of therapy side effects such as lung fibrosis. Using contrast-enhanced scans, fpVCT displayed the vascular trees of the brain, liver, and kidney down to the subsegmental level. Functional application of fpVCT in dynamic contrast-enhanced scans of the rat brain delivered physiologically reliable data of perfusion and tissue blood volume. Beyond scanning of small animal models as demonstrated here, fpVCT provides the ability to image animals up to the size of primates.

Dynamic contrast-enhanced magnetic resonance imaging rapidly indicates vessel regression in human squamous cell carcinomas grown in nude mice caused by VEGF receptor 2 blockade with DC101.

The purpose of our study was the investigation of early changes in tumor vascularization during antiangiogenic therapy with the vascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Subcutaneous heterotransplants of human skin squamous cell carcinomas in nude mice were treated with DC101. Animals were examined before and repeatedly during 2 weeks of antiangiogenic treatment using Gd-DTPA-enhanced dynamic T1-weighted MRI. With a two-compartment model, dynamic data were parameterized in "amplitude" (increase of signal intensity relative to precontrast value) and k(ep) (exchange rate constant). Data obtained by MRI were validated by parallel examinations of histological sections immunostained for blood vessels (CD31). Already 2 days after the first DC101 application, a decrease of tumor vascularization was observed, which preceded a reduction of tumor volume. The difference between treated tumors and controls became prominent after 4 days, when amplitudes of treated tumors were decreased by 61% (P =.02). In line with change of microvessel density, the decrease in amplitudes was most pronounced in tumor centers. On day 7, the mean tumor volumes of treated (153 +/- 843 mm(3)) and control animals (596 +/- 384 mm(3)) were significantly different (P =.03). After 14 days, treated tumors showed further growth reduction (83 +/- 93 mm(3)), whereas untreated tumors (1208 +/- 822 mm(3)) continued to increase (P =.02). Our data underline the efficacy of DC101 as antiangiogenic treatment in human squamous cell carcinoma xenografts in nude mice and indicate DCE MRI as a valuable tool for early detection of treatment effects before changes in tumor volume become apparent.

Dynamic magnetic resonance tomography and proton magnetic resonance spectroscopy of prostate cancers in rats treated by radiotherapy.

RATIONALE AND OBJECTIVES: To establish an experimental setting for monitoring perfusion and metabolism in orthotopic prostate cancer at 1.5 T using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) and 1H-MR spectroscopy (MRS). METHODS: Dunning rat prostate cancer cells were injected into the prostate by open surgery. Twelve tumor-bearing rats (5 of these irradiated) and 6 healthy controls were followed up using gadolinium-diethylenetriaminepentaacetic acid -enhanced dynamic MRI and 1H-MRS. Amplitude and the exchange rate constant kep were calculated (2-compartment model). From 1H-MR spectra, ratios of choline (Cho) and creatine (tCr) were calculated. All tumors were examined histologically. RESULTS: On DCE MRI parameter maps, tumors showed increased vascularization. kep and microvessel density were correlated (r = 0.97). Tumors showed elevated Cho/tCr and an unexpected lipid fraction (2.0-2.2 parts per million). Irradiation slowed tumor growth significantly. Changes of perfusion and metabolism could be detected in all tumors during follow up. CONCLUSION: DCE MRI and 1H-MRS has potential to characterize orthotopic Dunning prostate cancer in rats, which is a promising model similar to human prostate carcinomas.

Comparison of arterial spin-labeling techniques and dynamic susceptibility-weighted contrast-enhanced MRI in perfusion imaging of normal brain tissue.

OBJECTIVES: To evaluate relative cerebral blood flow (rCBF) in normal brain tissue using arterial spin-labeling (ASL) methods and first-pass dynamic susceptibility-weighted contrast-enhanced (DSC) magnetic resonance imaging (MRI). METHODS: Sixty-two patients with brain metastases were examined on a 1.5 T-system up to 6 times during routine follow-up after stereotactic radiosurgery. Perfusion values in normal gray and white matter were measured using the ASL techniques ITS-FAIR in 38 patients, Q2TIPS in 62 patients, and the first-pass DSC echo-planar (EPI) MRI after bolus administration of gadopentetate dimeglumine in 42 patients. Precision of the ASL sequences was tested in follow-up examinations in 10 healthy volunteers. RESULTS: Perfusion values in normal brain tissue obtained by all sequences correlated well by calculating Pearson's correlation coefficients (P < 0.0001) and remained unchanged after stereotactic radiosurgery as shown by analysis of variance (P > 0.05). CONCLUSION: Both ASL and DSC EPI MRI yield highly comparable perfusion values in normal brain tissue.

Assessment of irradiated brain metastases by means of arterial spin-labeling and dynamic susceptibility-weighted contrast-enhanced perfusion MRI: initial results.

RATIONALE AND OBJECTIVES: To assess if preradiation and early follow-up measurements of relative regional cerebral blood flow (rrCBF) can predict treatment outcome in patients with cerebral metastases and to evaluate rrCBF changes in tumor and normal tissue after stereotactic radiosurgery using arterial spin-labeling (ASL) and first-pass dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MRI. METHODS: In 25 patients with a total of 28 brain metastases, DSC MRI and ASL perfusion MRI using the Q2TIPS sequence were performed with a 1.5-T unit. Measurements were performed prior to and at 6 weeks, 12 weeks, and 24 weeks after stereotactic radiosurgery. Follow-up examinations were completely available in 25 patients for Q2TIPS and 17 patients with 18 metastases for DSC MRI. The rrCBF of the metastases and the normal brain tissue was determined by a region-of-interest analysis. rrCBF values were correlated with the treatment outcome that was classified according to tumor volume changes at 6 months. RESULTS: The alteration of the rrCBF at the 6-week follow-up was highly predictive for treatment outcome. A decrease of the rrCBF value predicted tumor response correctly in all metastases for Q2TIPS and in 13 of 16 metastases for DSC MRI. The pretherapeutic rrCBF was not able to predict treatment outcome. The rrCBF values in normal brain tissue affected by radiation doses less than 0.5 Gy remained unchanged after therapy. CONCLUSION: These preliminary results suggest that ASL and DSC MRI techniques determining rrCBF changes in brain metastases after stereotactic radiosurgery allow the prediction of treatment outcome.

Tumorsize dependent detection rate of endorectal MRI of prostate cancer--a histopathologic correlation with whole-mount sections in 70 patients with prostate cancer.

PURPOSE: To evaluate the value of T2w endorectal MRI (eMRI) for correct detection of tumor foci within the prostate regarding tumor size. MATERIALS AND METHODS: 70 patients with histologically proven prostate cancer were examined with T2w eMRI before radical prostatectomy at a 1.5T scanner. For evaluation of eMRI, two radiologists evaluated each tumor focus within the gland. After radical prostatectomy, the prostates were prepared as whole-mount sections, according to transversal T2w eMRI. For each slice, tumor surroundings were marked and compared with eMRI. Based on whole-mount section, 315 slices were evaluated and 533 tumor lesions were documented. RESULTS: Based on the T2w eMRI, 213 tumor lesions were described. In 137/213, histology could prove these lesions. EMRI was able to visualize 0/56 lesions with a maximum size of <0.3 cm (detection rate 0%), between 0.3 and 0.5 cm 4/116 (3%), between 1 and 0.5 cm 22/169 (13%), between 2 and 1cm 61/136 (45%) and for >2 cm 50/56 (89%). False positive eMRI findings were: <0.3 cm n=0, 0.5-0.3 cm n=12, 0.5-1cm n=34, 1-2 cm n=28 and >2 cm n=2. CONCLUSION: T2w eMRI cannot exclude prostate cancer with lesions smaller 10mm and 0.4 cm(3) respectively. The detection rate for lesions more than 20mm (1.6 cm(3)) is to be considered as high.

Simultaneous PET-MRI: a new approach for functional and morphological imaging.

Noninvasive imaging at the molecular level is an emerging field in biomedical research. This paper introduces a new technology synergizing two leading imaging methodologies: positron emission tomography (PET) and magnetic resonance imaging (MRI). Although the value of PET lies in its high-sensitivity tracking of biomarkers in vivo, it lacks resolving morphology. MRI has lower sensitivity, but produces high soft-tissue contrast and provides spectroscopic information and functional MRI (fMRI). We have developed a three-dimensional animal PET scanner that is built into a 7-T MRI. Our evaluations show that both modalities preserve their functionality, even when operated isochronously. With this combined imaging system, we simultaneously acquired functional and morphological PET-MRI data from living mice. PET-MRI provides a powerful tool for studying biology and pathology in preclinical research and has great potential for clinical applications. Combining fMRI and spectroscopy with PET paves the way for a new perspective in molecular imaging.

Morphologic, functional, and metabolic magnetic resonance imaging-guided prostate biopsy in a patient with prior negative transrectal ultrasound-guided biopsies and persistently elevated prostate-specific antigen levels.

A 65-year-old patient was examined with [11C]-choline positron emission tomography-computed tomography and magnetic resonance imaging (MRI) for possible tumor detection after two negative sessions of transrectal ultrasound-guided prostate biopsy and persistently elevated prostate-specific antigen levels for 27 months. Choline positron emission tomography revealed a small and circumscribed pathologic tracer uptake in the right dorsal peripheral gland. Whereas T2-weighted MRI and high b-value diffusion-weighted imaging were able to reproduce this suspicious area, proton MR spectroscopy showed no significant increase of the amplitude of choline-containing compounds. Magnetic resonance imaging-guided prostate biopsy was successfully performed. All specimens taken from the lesion showed a Gleason 5 tubular adenocarcinoma with low proliferative activity.

MRI-guided biopsy of the prostate increases diagnostic performance in men with elevated or increasing PSA levels after previous negative TRUS biopsies.

OBJECTIVES: Repeatedly negative prostate biopsies in individuals with elevated prostate specific antigen (PSA) levels can be frustrating for both the patient and the urologist. This study was performed to investigate if magnetic resonance imaging (MRI)-guided transrectal biopsy increases diagnostic performance in individuals with elevated or increasing PSA levels after previous negative conventional transrectal ultrasound (TRUS)-guided biopsies. METHODS: 27 consecutive men with a PSA >4 ng/ml and/or suspicious finding on digital rectal examination, suspicious MRI findings, and at least one prior negative prostate biopsy were included. Median age was 66 years (mean, 64.5+/-6.8); median PSA was 10.2 ng/ml (mean, 11.3+/-5.5). MRI-guided biopsy was performed with a closed unit at 1.5 Tesla, an MRI-compatible biopsy device, a needle guide, and a titanium double-shoot biopsy gun. RESULTS: Median prostate volume was 37.4 cm3 (mean, 48.4+/-31.5); median volume of tumor suspicious areas on T2w MR images was 0.83 cm3 (mean, 0.99+/-0.78). The mean number of obtained cores per patient was 5.22+/-1.45 (median, 5; range, 2-8). Prostate cancer was detected in 55.5% (15 of 27) of the men. MRI-guided biopsy could be performed without complications in all cases. CONCLUSION: According to our knowledge, this is the largest cohort of consecutive men to be examined by MRI-guided transrectal biopsy of the prostate in this setting. The method is safe, can be useful to select suspicious areas in the prostate, and has the potential to improve cancer detection rate in men with previous negative TRUS-biopsies.

3D proton MR spectroscopic imaging of prostate cancer using a standard spine coil at 1.5 T in clinical routine: a feasibility study.

The objective of this study was to demonstrate the feasibility of 3D proton MR spectroscopic imaging (MRSI) of the prostate using a standard spine instead of a dedicated endorectal coil at 1.5 T. Twenty-eight patients (25 with biopsy proven prostate cancers and three patients with a benign prostate hyperplasia) were examined. MRI and MRSI were conducted with commercial array surface coils at 1.5 T. Ratios of choline (Cho), creatine (Cr) and citrate (Ci) were calculated for tumour, central and peripheral zone retrospectively, based on axial T2 weighed MR images and histology reports. Prostate cancer was characterized by significantly elevated (Cho+Cr)/Ci ratio compared with non-tumourous prostate tissue. The quality of all proton MR spectra was considered to be good or acceptable in 17/28 patients (61%) and poor in 11/28 (39%) examinations. In 20/25 patients with proven malignancy (80%), MRSI was considered to be helpful for the detection of prostate cancer. In 4/25 patients with proven malignancy (16%) who underwent seed implantation, radiotherapy or hormone deprivation before MR examination spectroscopy was of poor and non-diagnostic quality. MRSI of the prostate is feasible within clinical routine using the spine array surface coil at 1.5 T. It can consequently be applied to patients even with contraindications for endorectal coils. However, spectral quality and signal-to-noise ratio is clearly inferior to 3D MRSI examinations with endorectal coils.