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 (> 4 ng/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, 1000 s/mm²) 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 (K_ax) and mean kurtosis (K_mean) were significantly different in the tumor (K_ax 1.78 ± 0.39, K_mean 1.84 ± 0.43) compared with the normal peripheral zone (K_ax 1.09 ± 0.12, K_mean 1.16 ± 0.13; p < 0.001) or the central gland (K_ax 1.40 ± 0.12, K_mean 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.     

Reference region extraction by clustering for the pharmacokinetic analysis of dynamic contrast-enhanced MRI in prostate cancer

PurposeDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measures changes in the concentration of an administered contrast agent to quantitatively evaluate blood circulation in a tumor or normal tissues. This method uses a pharmacokinetic analysis based on the time course of a reference region, such as muscle, rather than arterial input function. However, it is difficult to manually define a homogeneous reference region. In the present study, we developed a method for automatic extraction of the reference region using a clustering algorithm based on a time course pattern for DCE-MRI studies of patients with prostate cancer.MethodsTwo feature values related to the shape of the time course were extracted from the time course of all voxels in the DCE-MRI images. Each voxel value of T1-weighted images acquired before administration were also added as anatomical data. Using this three-dimensional feature vector, all voxels were segmented into five clusters by the Gaussian mixture model, and one of these clusters that included the gluteus muscle was selected as the reference region.ResultsEach region of arterial vessel, muscle, and fat was segmented as a different cluster from the tumor and normal tissues in the prostate. In the extracted reference region, other tissue elements including scattered fat and blood vessels were removed from the muscle region.ConclusionsOur proposed method can automatically extract the reference region using the clustering algorithm with three types of features based on the time course pattern and anatomical data. This method may be useful for evaluating tumor circulatory function in DCE-MRI studies.     

Quantitative MRI: Defining repeatability,reproducibility and accuracy for prostate cancer imaging biomarker development

IntroductionQuantitative MRI (qMRI) parameters have been increasingly used to develop predictive models to accurately monitor treatment response in prostate cancer after radiotherapy. To reliably detect changes in signal due to treatment response, predictive models require qMRI parameters with high repeatability and reproducibility. The purpose of this study was to measure qMRI parameter uncertainties in both commercial and in-house developed phantoms to guide the development of robust predictive models for monitoring treatment response.Materials and methodsADC, T1, and R2* values were acquired across three 3 T scanners with a prostate-specific qMRI protocol using the NIST/ISMRM system phantom, RSNA/NIST diffusion phantom, and an in-house phantom. A B1 field map was acquired to correct for flip angle inhomogeneity in T1 maps. All sequences were repeated in each scan to assess within-session repeatability. Weekly scans were acquired on one scanner for three months with the in-house phantom. Between-session repeatability was measured with test-retest scans 6-months apart on all scanners with all phantoms. Accuracy, defined as percentage deviation from reference value for ADC and T1, was evaluated using the system and diffusion phantoms. Repeatability and reproducibility coefficients of variation (%CV) were calculated for all qMRI parameters on all phantoms.ResultsOverall, repeatability CV of ADC was <2.40%, reproducibility CV was <3.98%, and accuracy ranged between −8.0% to 2.7% across all scanners. Applying B1 correction on T1 measurements significantly improved the repeatability and reproducibility (p<0.05) but increased error in accuracy (p<0.001). Repeatability and reproducibility of R2* was <4.5% and <7.3% respectively in the system phantom across all scanners.ConclusionRepeatability, reproducibility, and accuracy in qMRI parameters from a prostate-specific protocol was estimated using both commercial and in-house phantoms. Results from this work will be used to identify robust qMRI parameters for use in the development of predictive models to longitudinally monitor treatment response for prostate cancer in current and future clinical trials.     

Diffusion-weighted MRI in prostate cancer -- comparison between single-shot fast spin echo and echo planar imaging sequences

Diffusion-weighted (DW) MRI at 1.5 T was carried out in two groups of patients. MRI data were correlated with the biopsy and histopathology (where available). The performance of two sequences -- a single-shot FSE (14 patients) and a single-shot EPI (15 patients) -- was compared. Average ADC values from the normal peripheral zone (PZ), central gland (CG) and the tumour [prostate carcinoma (PCa)] were calculated from b values of 0 and 600. Tukey-Kramer test was used for statistical analysis. EPI produced higher values of ADC (10(-3) mm(2)/s) than FSE sequence: 1.992+/-0.208 vs. 1.573+/-0.270 in PZ (P<.001), 1.518+/-0.126 vs. 1.373+/-0.179 in CG and 1.214+/-0.254 vs. 0.993+/-0.158 in PCa (P<.01). In conclusion, both EPI and FSE sequences showed differences in ADC between normal PZ, CG and PCa; however, EPI produced significantly higher ADC values than FSE.     

Claustrophobia in MRI: the role of cognitions

Purpose

This study aimed to investigate the role of cognitive and behavioural factors in the experience of claustrophobia in the context of magnetic resonance imaging (MRI) scanners.

Materials and Methods

One hundred and thirty outpatients attending an MRI unit completed questionnaires before and after their scans. Specific measures of experience in the scanner included subjective anxiety, panic symptoms, strategies used to stay calm and negative cognitions (such as ‘I will suffocate’ and ‘I am going to faint in here’). Other general measures used included anxiety, depression, health anxiety and fears of restriction and suffocation.

Results

The amount of anxiety experienced during the scan was related to the perceived amount of time spent having physical symptoms of panic. Cognitions reported concerned the following: suffocation, harm caused by the machine and lack of perceived control. The number of strategies patients used to cope in the machine was also a related factor. Neither position in the scanner, nor head coil use nor previous experience of being in the scanner was related to levels of anxiety.

Conclusion

The cognitions identified here may be used to construct a measure to identify those unable to enter the scanner or those most likely to become claustrophobic whilst undergoing the procedure and to further inform future brief, effective interventions.     

Differentiation of bone metastases from prostate cancer and benign red marrow depositions of the pelvic bone with multiparametric MRI

PurposeTo investigate the diagnostic utilities of imaging parameters derived from T1-weighted imaging (T1WI), diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to differentiate bone metastases from prostate cancer and benign red marrow depositions of the pelvic bone.Materials and methodsThirty-six lesions from 36 patients with prostate cancer were analyzed with T1WI, DWI, and DCE-MRI. The lesions were classified in the bone metastases (n = 22) and benign red marrow depositions (n = 14). Lesion-muscle ratio (LMR), apparent diffusion coefficient (ADC), volume transfer constant (K^trans), reflux rate (Kep), and volume fraction of the extravascular extracellular matrix (Ve) values were obtained from the lesions. The imaging parameters of the both groups were compared using the Mann-Whitney U test, receiver operating characteristics (ROC) curves were analyzed. For the ROC curves, area under the curves (AUCs) were compared.ResultsThe ADC, K^trans, K_ep, and V_e values of bone metastases were significantly higher than those of benign red marrow depositions (Mann-Whitney U test, p < 0.05). However, there was no significant difference in LMR between the two groups (Mann-Whitney U test, p = 0.360). The AUCs of K^trans_, K_ep, ADC, V_e, and LMR were 0.896, 0.844, 0.812, 0.724, and 0.448, respectively. In the pairwise comparison of ROC curves, the AUCs of K^trans and K_ep was significantly higher than LMR.ConclusionsK^trans, K_ep, V_e, and ADC values can be used as imaging tools to differentiate bone metastases from prostate cancer and benign red marrow depositions of the pelvic bone.     

Biexponential apparent diffusion coefficients in prostate cancer

Purpose

The purpose of this study was to investigate the need for biexponential signal decay modeling for prostate cancer diffusion signal decays with b-factor over an extended b-factor range.

Materials and Methods

Ten healthy volunteers and 12 patients with a bulky prostate cancer underwent line scan diffusion-weighted MR imaging in which b-factors from 0 to 3000 s/mm² in 16 steps were sampled. The acquired signal decay curves were fit with both monoexponential and biexponential signal decay functions and a statistical comparison between the two fits was performed.

Results

The biexponential model provided a statistically better fit over the monoexponential model on the peripheral zone (PZ), transitional zone (TZ) and prostate cancer. The fast and slow apparent diffusion coefficients (ADCs) in the PZ, TZ and cancer were 2.9±0.2, 0.7±0.2×10⁻³ mm²/ms (PZ); 2.9±0.4, 0.7±0.2×10⁻³ mm²/ms (TZ); and 1.7±0.4, 0.3±0.1×10⁻³ mm²/ms (cancer), respectively. The apparent fractions of the fast diffusion component in the PZ, TZ and cancer were 70±10%, 60±10% and 50±10%, respectively. The fast and slow ADCs of cancer were significantly lower than those of TZ and PZ, and the apparent fraction of the fast diffusion component was significantly smaller in cancer than in PZ.

Conclusions

Biexponential diffusion decay functions are required for prostate cancer diffusion signal decay curves when sampled over an extended b-factor range, providing additional, unique tissue characterization parameters for prostate cancer.     

The study on changes of rectum area in proton prostate cancer therapy

The purpose of this study is to determine the changes in the rectum area during treatment and to identify the rectum area within the given field of view in order to reproduce the same pose as that presented during therapy planning to properly deliver the planned dose to the prostate. We obtained digitally reconstructed radiographs after planning treatment for 30 patients out of all patients who had been subjected to proton prostate cancer therapy from August 2012 to November 2014 at this hospital. We then obtained an image using a digital imaging positioning system (DIPS) on the first day of treatment. When planning the digitally reconstructed radiograph treatment, we determined the change in size of the rectum between the actual treatment and treatment planning by measuring the cross section of the rectum and the cross section on the image from the DIPS. The results indicated that the rectum area in the digitally reconstructed radiograph taken during treatment planning and the rectum area obtained from the DIPS image during treatment were different. As a consequence, when region targeted for proton treatment of prostate cancer does not maintain a constant volume, the position of the prostate does not receive an adequate dose due to such changes. Therefore, the results of this study will be useful to determine the corresponding volume during a prostate treatment plan.     

Histopathological analysis of a bladder cancer stalk observed on MRI

Papillary transitional cell carcinoma of the bladder has a loose connective tissue stalk. For staging of bladder cancer on magnetic resonance imaging (MRI), it is important to clearly separate the cancer from the bladder wall. It is possible to distinguish a stalk from the cancer by the difference of intensity on the using MRI. Sixteen stalks of 20 polypoid bladder tumors on any of the T(2)W(I), dynamic images and delayed enhanced images were demonstrated. Most of the stalks show lower signal intensity than the tumors on T(2)W(I), less enhancement on dynamic images and stronger enhancement on delayed enhanced images. The stalk consisted of fibrous connective tissue, capillary blood vessels, inflammatory cell infiltration and edema. This stalk extended from the bladder wall to the center of the tumor. Some of the superficial muscular bundles were pulled into the stalk. These histopathological findings were compatible with the patterns of signal intensities on MRI. The identification of the stalk of a polypoid tumor may be an important observation to exclude bladder wall invasion by tumor.     

Diagnostic value of breast MRI for predicting metastatic axillary lymph nodes in breast cancer patients: diffusion-weighted MRI and conventional MRI

Purposes

To evaluate the diagnostic value of diffusion-weighted MRI (DWI) and combination of conventional MRI and DWI to predict metastatic axillary lymph nodes in breast cancer.

Materials and methods

Two hundred fifty-two breast cancer patients with 253 axillae were included. The morphological parameters on axial T2-weighted images without fat saturation and apparent diffusion coefficient (ADC) values were retrospectively analyzed. An independent t-test/chi-square test and receiver operating characteristics (ROC) curve analysis were used.

Results

On conventional MRI, short and long axis length, maximal cortical thickness, relative T2 value, loss of fatty hilum (p < 0.001 for each), and eccentric cortical thickening (p < 0.003) were statistically significantly different between the metastatic and nonmetastatic groups. The short axis to long axis ratio was not a statistically significant parameter. The ADC value was significantly different between the 2 groups, with an AUC that was higher than that of conventional MR parameters (AUC, 0.815; threshold, ≤ 0.986 × 10–3 mm²/sec; sensitivity, 75.8%; specificity, 83.9%). Using the adopted thresholds for each parameter, a total number of findings suggesting malignancy of 4 or higher was determined as the threshold, with high specificity (90.1%).

Conclusion

Using conventional MRI and DWI, we can evaluate the axilla in breast cancer with high specificity.     

ToF-SIMS PC-DFA analysis of prostate cancer cell lines

Three closely related cancer cell lines have been analysed with ToF-SIMS using a C₆₀⁺ primary ion beam. Principal component-discriminant function analysis (PC-DFA) has been applied for spectral classification. Various spectral pre-processing methods are discussed and assessed for optimum discrimination of this data set. The sum-normalised PC-DFA spectral model produced sensitivities as high as 83.3% and specificities as high as 100% at the 99% confidence limit. At this confidence limit only one errant spectrum was misclassified. The resulting loadings plots suggest that a range of lipid and amino-acid related signals are responsible for the cell line discrimination.     

Non-Gaussian water diffusion kurtosis imaging of prostate cancer

Purpose

To evaluate the non-Gaussian water diffusion properties of prostate cancer (PCa) and determine the diagnostic performance of diffusion kurtosis (DK) imaging for distinguishing PCa from benign tissues within the peripheral zone (PZ), and assessing tumor lesions with different Gleason scores.

Materials and Methods

Nineteen patients who underwent diffusion weighted (DW) magnetic resonance imaging using multiple b-values and were pathologically confirmed with PCa were enrolled in this study. Apparent diffusion coefficient (ADC) was derived using a monoexponential model, while diffusion coefficient (D) and kurtosis (K) were determined using a DK model. Differences between the ADC, D and K values of benign PZ and PCa, as well as those of tumor lesions with Gleason scores of 6, 7 and ≥ 8 were assessed. Correlations between parameters D and K in PCa were analyzed using Pearson’s correlation coefficient. ADC, D and K values were correlated with Gleason scores of 6, 7 and ≥ 8, respectively.

Results

ADC and D values were significantly (p < 0.001) lower in PCa (0.79 ± 0.14 μm²/ms and 1.56 ± 0.23 μm²/ms, respectively) compared to benign PZ (1.23 ± 0.19 μm²/ms and 2.54 ± 0.24 μm²/ms, respectively). K values were significantly (p < 0.001) greater in PCa (0.96 ± 0.20) compared to benign PZ (0.59 ± 0.08). D and K showed fewer overlapping values between benign PZ and PCa compared to ADC. There was a strong negative correlation between D and K values in PCa (Pearson correlation coefficient r = − 0.729; p < 0.001). ADC and K values differed significantly in tumor lesions with Gleason scores of 6, 7 and ≥ 8 (p < 0.001 and p = 0.001, respectively), although no significant difference was detected for D values (p = 0.325). Significant correlations were found between the ADC value and Gleason score (r = − 0.828; p < 0.001), as well as the K value and Gleason score (r = 0.729; p < 0.001).

Conclusion

DK model may add value in PCa detection and diagnosis. K potentially offers a new metric for assessment of PCa.     

MRI of intracranial sinovenous thrombosis: the role of phase imaging

Conventional spin-echo magnetic resonance (MR) imaging of venous thrombosis is complicated by the variable appearance produced by the stage of blood clot degradation and velocity of blood flow. Phase MR imaging is a simple method based primarily on whether protons are stationary or moving. A case of superior sagittal sinus thrombosis demonstrates the utility of phase imaging.     

Carr-Purcell-Meiboom-Gill imaging of prostate cancer: quantitative T2 values for cancer discrimination

Quantitative, apparent T(2) values of suspected prostate cancer and healthy peripheral zone tissue in men with prostate cancer were measured using a Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence in order to assess the cancer discrimination potential of tissue T(2) values. The CPMG imaging sequence was used to image the prostates of 18 men with biopsy-proven prostate cancer. Whole gland coverage with nominal voxel volumes of 0.54 x 1.1 x 4 mm(3) was obtained in 10.7 min, resulting in data sets suitable for generating high-quality images with variable T(2)-weighting and for evaluating quantitative T(2) values on a pixel-by-pixel basis. Region-of-interest analysis of suspected healthy peripheral zone tissue and suspected cancer, identified on the basis of both T(1)- and T(2)-weighted signal intensities and available histopathology reports, yielded significantly (P<.0001) longer apparent T(2) values in suspected healthy tissue (193+/-49 ms) vs. suspected cancer (100+/-26 ms), suggesting potential utility of this method as a tissue specific discrimination index for prostate cancer. We conclude that CPMG imaging of the prostate can be performed in reasonable scan times and can provide advantages over T(2)-weighted fast spin echo (FSE) imaging alone, including quantitative T(2) values for cancer discrimination as well as proton density maps without the point spread function degradation associated with short effective echo time FSE sequences.     

Evaluation of the role of magnetization transfer imaging in prostate: a preliminary study

Results of the preliminary study on the evaluation of the role of magnetization transfer imaging (MTI) of prostate in men who had raised prostate-specific antigen (PSA) (>4 ng/ml) or abnormal digital rectal examination (DRE) are reported. MT ratio (MTR) was calculated for 20 patients from the hyper- (normal) and hypo-intense regions (area suspicious of malignancy as seen on T2-weighted MRI) of the peripheral zone (PZ) and the central gland (CG) at 1.5 T. In addition, MTR was calculated for three healthy controls. Mean MTR was also calculated for the whole of the PZ (including hyper- and hypo-intense area) in all patients. Out of 20 patients, biopsy revealed malignancy in 12 patients. Mean MTR value (8.29+/-3.49) for the whole of the PZ of patients who were positive for malignancy on biopsy was statically higher than that observed for patients who were negative for malignancy (6.18+/-3.15). The mean MTR for the whole of the PZ of controls was 6.18+/-1.63 and is similar to that of patients who were negative for malignancy. Furthermore, for patients who showed hyper- (normal portion) and hypo-intense (region suspicious of malignancy) regions of the PZ, the MTR was statistically significantly different. These preliminary results reveal the potential role of MT imaging in the evaluation of prostate cancer.     

Investigation of prostate cancer using diffusion-weighted intravoxel incoherent motion imaging

Purpose

The objective of this work was to evaluate the diagnostic performance of the intravoxel incoherent motion (IVIM) model to differentiate between healthy and malignant prostate tissue.

Materials and Methods

Regions of interest were drawn in healthy and cancerous tissue of 13 patients with histologically proven prostate carcinoma and fitted to a monoexponential model [yielding the apparent diffusion coefficient (ADC)] and the IVIM signal equation (yielding the perfusion fraction f, the diffusion constant D and the pseudodiffusion coefficient of perfusion D?). Parameter maps were calculated for all parameters.

Results

The ADC, D and f were significantly (P<.005) lowered in cancerous tissue (1.01±0.22 μm²/ms, 0.84±0.19 μm²/ms and 14.27±7.10%, respectively) compared to benign tissue (1.49±0.17 μm²/ms, 1.21±0.22 μm²/ms and 21.25±8.32%, respectively). Parameter maps of D and f allowed for a delineation of the tumor, but showed higher variations compared to the ADC map.

Conclusion

Apparent diffusion coefficient maps provide better diagnostic performance than IVIM maps for tumor detection. However, the results suggest that the reduction of the ADC in prostate cancer stems not only from changes in cellularity but also from perfusion effects. IVIM imaging might hold promise for the diagnosis of other prostatic lesions.     

Photo-activated pheophorbide a inhibits the growth of prostate cancer cells

Pheophorbide a (PhA) was identified as a photosensitizer to exert cytotoxicity on tumor cells. However, the efficacy of this compound on the treatment of prostate cancer remains unknown. The aim of this study was to evaluate the photodynamic effect of PhA on prostate cancer cells. Cellular uptake of PhA and cell viability after photo-activation was studied in LNCaP prostate cancer cells. The corresponding production of reactive oxygen species within cells was determined after photodynamic therapy (PDT). Our results showed that the uptake of PhA into LNCaP cells was in a time-dependent manner and the cytotoxicity of PhA-PDT was photosensitizer dose- and light dose-dependent. The intracellular reactive oxygen species was remarkably induced after PDT treatment, which was responsible for the inhibition effect on prostate cancer cells. This is the first report to evaluate the photodynamic effect of PhA on prostate cancer. Our findings demonstrate that PhA-PDT may be a potentially promising treatment for localized prostate cancer, which can be a therapeutic option after the failures of radiotherapy and hormone therapy.