Michael Quentin

Prospective Randomized Trial Comparing Magnetic Resonance Imaging (MRI)-guided In-bore Biopsy to MRI-ultrasound Fusion and Transrectal Ultrasound-guided Prostate Biopsy in Patients with Prior Negative Biopsies

BACKGROUND A significant proportion of prostate cancers (PCas) are missed by conventional transrectal ultrasound-guided biopsy (TRUS-GB). It remains unclear whether the combined approach using targeted magnetic resonance imaging (MRI)-ultrasound fusion-guided biopsy (FUS-GB) and systematic TRUS-GB is superior to targeted MRI-guided in-bore biopsy (IB-GB) for PCa detection. OBJECTIVE To compare PCa detection between IB-GB alone and FUS-GB + TRUS-GB in patients with at least one negative TRUS-GB and prostate-specific antigen ≥4 ng/ml. DESIGN, SETTING, AND PARTICIPANTS Patients were prospectively randomized after multiparametric prostate MRI to IB-GB (arm A) or FUS-GB + TRUS-GB (arm B) from November 2011 to July 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The study was powered at 80% to demonstrate an overall PCa detection rate of ≥60% in arm B compared to 40% in arm A. Secondary endpoints were the distribution of highest Gleason scores, the rate of detection of significant PCa (Gleason ≥7), the number of biopsy cores to detect one (significant) PCa, the positivity rate for biopsy cores, and tumor involvement per biopsy core. RESULTS AND LIMITATIONS The study was halted after interim analysis because the primary endpoint was not met. The trial enrolled 267 patients, of whom 210 were analyzed (106 randomized to arm A and 104 to arm B). PCa detection was 37% in arm A and 39% in arm B (95% confidence interval for difference, -16% to 11%; p=0.7). Detection rates for significant PCa (29% vs 32%; p=0.7) and the highest percentage tumor involvement per biopsy core (48% vs 42%; p=0.4) were similar between the arms. The mean number of cores was 5.6 versus 17 (p<0.001). A limitation is the limited number of patients because of early cessation of accrual. CONCLUSIONS This trial failed to identify an important improvement in detection rate for the combined biopsy approach over MRI-targeted biopsy alone. A prospective comparison between MRI-targeted biopsy alone and systematic TRUS-GB is justified. PATIENT SUMMARY Our randomized study showed similar prostate cancer detection rates between targeted prostate biopsy guided by magnetic resonance imaging and the combination of targeted biopsy and systematic transrectal ultrasound-guided prostate biopsy. An important improvement in detection rates using the combined biopsy approach can be excluded.

Comparison of different mathematical models of diffusion-weighted prostate MR imaging

PURPOSE To evaluate which mathematical model (monoexponential, biexponential, statistical, kurtosis) fits best to the diffusion-weighted signal in prostate magnetic resonance imaging (MRI). MATERIALS AND METHODS 24 prostate 3-T MRI examinations of young volunteers (YV, n=8), patients with biopsy proven prostate cancer (PC, n=8) and an aged matched control group (AC, n=8) were included. Diffusion-weighted imaging was performed using 11 b-values ranging from 0 to 800 s/mm(2). RESULTS Monoexponential apparent diffusion coefficient (ADC) values were significantly (P<.001) lower in the peripheral (PZ) zone (1.18±0.16 mm(2)/s) and the central (CZ) zone (0.73±0.13 mm(2)/s) of YV compared to AC (PZ 1.92±0.17 mm(2)/s; CZ 1.35±0.21 mm(2)/s). In PC ADC(mono) values (0.61±0.06 mm(2)/s) were significantly (P<.001) lower than in the peripheral of central zone of AC. Using the statistical analysis (Akaike information criteria) in YV most pixels were best described by the biexponential model (82%), the statistical model, respectively kurtosis (93%) each compared to the monoexponential model. In PC the majority of pixels was best described by the monoexponential model (57%) compared to the biexponential model. CONCLUSION Although a more complex model might provide a better fitting when multiple b-values are used, the monoexponential analyses for ADC calculation in prostate MRI is sufficient to discriminate prostate cancer from normal tissue using b-values ranging from 0 to 800 s/mm(2).

Temporally resolved electrocardiogram-triggered diffusion-weighted imaging of the human kidney: correlation between intravoxel incoherent motion parameters and renal blood flow at different time points of the cardiac cycle.

Purpose:To evaluate the influence of pulsatile blood flow on apparent diffusion coefficients (ADC) and the fraction of pseudodiffusion (FP) in the human kidney. Materials and Methods:The kidneys of 6 healthy volunteers were examined by a 3-T magnetic resonance scanner. Electrocardiogram (ECG)-gated and respiratory-triggered diffusion-weighted imaging (DWI) and phase-contrast flow measurements were performed. Flow imaging of renal arteries was carried out to quantify the dependence of renal blood flow on the cardiac cycle. ECG-triggered DWI was acquired in the coronal plane with 16 b values in the range of 0 s/mm2 and 750 s/mm2 at the time of minimum (MIN) (20 milliseconds after R wave) and maximum renal blood flow (MAX) (197 ± 24 milliseconds after R wave). The diffusion coefficients were calculated using the monoexponential approach as well as the biexponential intravoxel incoherent motion model and correlated to phase-contrast flow measurements. Results:Flow imaging showed pulsatile renal blood flow depending on the cardiac cycle. The mean flow velocity at MIN was 45 cm/s as compared with 61 cm/s at MAX. Fp at MIN (0.29) was significantly lower than at MAX (0.40) (P = 0.001). Similarly, ADCmono, derived from the monoexponential model, also showed a significant difference (P < 0.001) between MIN (ADCmono = 2.14 ± 0.08 × 10−3 mm2/s) and MAX (ADCmono = 2.37 ± 0.04 × 10−3 mm2/s). The correlation between renal blood flow and Fp (r = 0.85) as well as ADCmono (r = 0.67) was statistically significant. Conclusion:Temporally resolved ECG-gated DWI enables for the determination of the diffusion coefficients at different time points of the cardiac cycle. ADCmono and FP vary significantly among acquisitions at minimum (diastole) and maximum (systole) renal blood flow. Temporally resolved ECG-gated DWI might therefore serve as a novel technique for the assessment of pulsatility in the human kidney.

Predictive power of the ESUR scoring system for prostate cancer diagnosis verified with targeted MR-guided in-bore biopsy

PURPOSE This study evaluates the diagnostic value of the ESUR scoring system (PI-RADS) regarding prostate cancer detection using MR-guided in-bore biopsies (IB-GB) as the reference standard. METHODS 566 lesions in 235 consecutive patients (65.7 ± 7.9 years, PSA 9.9 ± 8.5 ng/ml) with a multiparametric (mp)-MRI (T2WI, DWI, DCE) of the prostate at 3T were scored using the PI-RADS scoring system. PI-RADS single (PSsingle), summed (PSsum), and overall (PSoverall) scores were determined. All lesions were histologically verified by IB-GB. RESULTS Lesions with a PSsum below 9 contained no prostate cancer (PCa) with Gleason score (GS) ≥ 4+3=7. A PSsum of 13-15 (PSoverall V) resulted in 87.8% (n=108) in PCa and in 42.3% (n=52) in GS ≥ 4+3=7. Transition zone (TZ) lesions with a PSsum of 13-15 (PSoverall V) resulted in 76.3% (n=36) in PCa and in 26.3% (n=10) in GS ≥ 4+3=7, whereas for peripheral zone (PZ) lesions cancer detection rate at this score was 92.9% (n=79) and 49.4% (n=42) for GS ≥ 4+3=7. Using a threshold of PSsum ≥ 10, sensitivity was 86.0%, and negative predictive value (NPV) was 86.2%. For higher grade PCa sensitivity was 98.6%, and NPV was 99.5%. CONCLUSION A PSsum below 9 excluded a higher grade PCa, whereas lesions with a PSsum ≥ 13 (PSoverall V) represented in 88% PCa, and in 42% higher grade PCa. The PSsum or PSoverall demonstrated a better diagnostic value for PZ lesions with higher detection rates for higher grade PCa compared to TZ lesions.

Feasibility of diffusional kurtosis tensor imaging in prostate MRI for the assessment of prostate cancer: preliminary results.

PURPOSE To assess the feasibility of full diffusional kurtosis tensor imaging (DKI) in prostate MRI in clinical routine. Histopathological correlation was achieved by targeted biopsy. MATERIALS AND METHODS Thirty-one men were prospectively included in the study. Twenty-one were referred to our hospital with increased prostate specific antigen (PSA) values (>4ng/ml) and suspicion of prostate cancer. The other 10 men were volunteers without any history of prostate disease. DKI applying diffusion gradients in 20 different spatial directions with four b-values (0, 300, 600, 1000s/mm(2)) was performed additionally to standard functional prostate MRI. Region of interest (ROI)-based measurements were performed in all histopathologically verified lesions of every patient, as well as in the peripheral zone, and the central gland of each volunteer. RESULTS DKI showed a substantially better fit to the diffusion-weighted signal than the monoexponential apparent diffusion coefficient (ADC). Altogether, 29 lesions were biopsied in 14 different patients with the following results: Gleason score 3+3=6 (n=1), 3+4=7 (n=7), 4+3=7 (n=6), 4+4=8 (n=1), and 4+5=9 (n=2), and prostatitis (n=12). Values of axial (Kax) and mean kurtosis (Kmean) were significantly different in the tumor (Kax 1.78±0.39, Kmean 1.84±0.43) compared with the normal peripheral zone (Kax 1.09±0.12, Kmean 1.16±0.13; p<0.001) or the central gland (Kax 1.40±0.12, Kmean 1.44±0.17; p=0.01 respectively). There was a minor correlation between axial kurtosis (r=0.19) and the Gleason score. CONCLUSION Full DKI is feasible to utilize in a routine clinical setting. Although there is some overlap some DKI parameters can significantly distinguish prostate cancer from the central gland or the normal peripheral zone. Nevertheless, the additional value of DKI compared with conventional monoexponential ADC calculation remains questionable and requires further research.

MRI-Guided In-Bore Biopsy: Differences Between Prostate Cancer Detection and Localization in Primary and Secondary Biopsy Settings

OBJECTIVE The objective of our study was to evaluate transrectal MRI-guided in-bore biopsy in patients who either were biopsy-naive (primary biopsy) or had undergone at least one previous negative transrectal ultrasound-guided biopsy (secondary biopsy) with regard to cancer detection rate, tumor localization, and lesion size. MATERIALS AND METHODS In total, 1602 biopsy cores from 297 consecutive patients (mean ± SD, 66.1 ± 7.8 years; median prostate-specific antigen value, 8.2 ng/mL) in primary (n = 160) and secondary (n = 137) prostate biopsy settings were evaluated in this retrospective study. All patients previously underwent prostate MRI (T2-weighted imaging, DWI, dynamic contrast-enhanced imaging) at 3 T. All described lesions were biopsied with MRI-guided in-bore biopsy and were examined histologically. RESULTS In 148 patients, overall 511 cores were positive for prostate cancer. Clinically significant prostate cancer (any Gleason pattern ≥ 4) was found in 82.4% of patients. The prostate cancer detection rate for patients who underwent primary biopsies was 55.6% and was 43.1% for patients who underwent secondary biopsies. In patients with primary versus secondary biopsies, prostate cancer was located peripherally in 62.9% versus 49.5% (p = 0.04), in the transition zone in 27.4% versus 27.5% (p = 1.0), and in the anterior stroma in 10.3% versus 22.9% (p < 0.01), respectively. The prostate cancer detection rates for patients with smaller prostate volumes (< 30 vs 30-50 vs > 50 mL; p < 0.01) or for patients with larger lesions (> 0.5 vs 0.25-0.5 vs < 0.25 cm(3); p < 0.01) were significantly higher. CONCLUSION MRI-guided in-bore biopsy led to high detection rates in primary and secondary prostate biopsies. Prostate cancer detection rates were significantly higher for patients with larger lesions and smaller prostate glands. In patients who underwent secondary biopsies, prostate cancer was located in the anterior stroma at a significantly more frequent rate.

Impact of blood flow on diffusion coefficients of the human kidney: A time-resolved ECG-triggered diffusion-tensor imaging (DTI) study at 3T

To evaluate the impact of renal blood flow on apparent diffusion coefficients (ADC) and fractional anisotropy (FA) using time‐resolved electrocardiogram (ECG)‐triggered diffusion‐tensor imaging (DTI) of the human kidneys.

Gender, BMI and T2 dependencies of glycosaminoglycan chemical exchange saturation transfer in intervertebral discs

PURPOSE The purpose was to investigate the dependence of glycosaminoglycan chemical exchange saturation transfer (gagCEST) effect of lumbar intervertebral discs (IVD) on gender, body mass index and T2 value. METHODS T2 imaging and gagCEST imaging was performed in 34 healthy volunteers (17 males, 17 females) without low back pain at a 3T MRI system (Magnetom Trio, A Tim System, Siemens Healthcare, Erlangen, Germany). The body mass index was determined for each volunteer. The mean and standard deviation of MTRasym and T2 values were calculated for nucleus pulposus (NP) and annulus fibrosus (AF) as descriptive statistics for females and males. An unpaired students t-test was applied in order to validate obtained differences. Pearson correlation was determined in order to reveal, if gagCEST effect and T2 values decrease with increasing body mass index (BMI). Pearson correlation analysis was additionally performed between gagCEST and T2 values. RESULTS GagCEST effect and T2 values were significantly higher in females compared to males [gagCEST effect (nucleus pulposus, females)=3.58±1.49%; gagCEST effect (nucleus pulosus, males)=3.01±1.63%, p-value (gagCEST effect, nucleus pulposus)=0.02); T2 (nucleus pulposus, females)=134.56±30.27 ms, T2 (nucleus pulposus, males)=122.35±27.64 ms, p-value (T2, nucleus pulposus)=0.01)]. Pearson correlation analysis showed a significant negative relation between BMI and gagCEST effect (nucleus pulposus: ρ=-0.16, p=0.03) and between BMI and T2 values (nucleus pulposus: ρ=-0.30, p<0.01). The correlation between gagCEST effect and T2-values was highly significant (nucleus pulposus: ρ=0.59, p<0.01). CONCLUSIONS Significantly lower gagCEST effects were found in males compared to females and with increased body mass index. The gagCEST effect was highly correlated with quantitative T2 imaging.

Diffusion-weighted imaging (DWI) of the spleen in patients with liver cirrhosis and portal hypertension.

OBJECTIVE The purpose of this study was to assess the influence of liver cirrhosis and portal hypertension on diffusion coefficients of the spleen. MATERIAL AND METHODS We retrospectively evaluated 50 patients with liver cirrhosis and 50 patients without any history of liver disease who underwent magnetic resonance imaging of the upper abdomen, including echo planar diffusion-weighted imaging using b values of 50, 300 and 600mm(2)/s. Spleen apparent diffusion coefficient (ADC), liver ADC, muscle ADC and normalized spleen ADC (defined as the ratio of spleen ADC to muscle ADC) were compared between cirrhotic patients and patients in the control group and correlated with Child-Pugh stages. Reproducibility was assessed by measuring interclass correlation coefficient (n=11). Additionally, in eight patients, ADC measurements were performed 1 day before and 3 days after transjugular intrahepatic portosystemic shunt (TIPSS) implantation. RESULTS Compared with control subjects, patients with cirrhosis and portal hypertension had significantly higher spleen ADCs (P=.0001). There was a statistically significant correlation between Child-Pugh grade and spleen ADC (Pearson correlation coefficient, observer 1 r=0.6, P=.0001; observer 2 r=0.5, P=.0001). After TIPSS implantation, we observed a reduction in spleen ADC values. Spleen ADC measurements showed a high reproducibility (interclass correlation coefficient 0.75, P=.001). CONCLUSION Our data suggest that different stages of liver cirrhosis and portal hypertension correlate with ADC values of the spleen. Furthermore, ADC values of the spleen decrease after TIPSS implantation. Further studies are required to understand the potential clinical values of these observations.

Magnetic resonance imaging of the prostate at 1.5 versus 3.0 T: A prospective comparison study of image quality

OBJECTIVES This study prospectively evaluates objective image quality (IQ), subjective IQ, and PI-RADS scoring of prostate MRI at 3.0T (3T) and 1.5T (1.5T) within the same patients. METHODS Sixty-three consecutive patients (64±9years) were prospectively included in this non-inferiority trial, powered at 80% to demonstrate a ≤10% difference in signal-to-noise (SNR) and contrast-to-noise ratio (CNR) of T2-weighted and diffusion-weighted imaging (T2WI, DWI) at 1.5T compared to 3T. Secondary endpoints were analysis of subjective IQ and PI-RADS v2 scoring. RESULTS All patients received multi-parametric prostate MRI on a 3T (T2WI, DWI, DCE) and bi-parametric MRI (T2WI, DWI) on a 1.5T scanner using body coils, respectively. SNR and CNR of T2WI were similar at 1.5T and 3T (p=0.7-1), but of DWI significantly lower at 1.5T (p<0.01). Subjective IQ was significantly better at 3T for both, T2WI and DWI (p<0.01). PI-RADS scores were comparable for both field strengths (p=0.05-1). Inter-reader agreement was excellent for subjective IQ assessment and PI-RADS scoring (k=0.9-1). CONCLUSION Prostate MRI at 1.5T can reveal comparable objective image quality in T2WI, but is inferior to 3T in DWI and subjective IQ. However, similar PI-RADS scoring and thus diagnostic performance seems feasible independent of the field strength even without an endorectal coil.