In vivo differential diagnosis of prostate cancer and benign prostatic hyperplasia: localized proton magnetic resonance spectroscopy using external-body surface coil

Localized proton-stimulated echo acquisition mode (STEAM) spectroscopy was performed in seven patients with benign prostatic hyperplasia (BPH), six patients with prostate cancer, and seven healthy volunteers to determine whether citrate levels detected using a saddle-type external-body surface coil (two loops of 13 cm ×17 cm) could reliably discriminate BPH from prostatic cancer. Relative area ratios of citrate level to choline plus creatine or citrate to lipid signal were compared with postoperative pathologic histology findings. The metabolic signals were well detectable as much as the line width of water resonance was ranging from 5 to 9 hz. Average SNRs of citrate in BPH and prostate cancer were 11.4 and 1.9, respectively. The major finding was consistently lower citrate levels in prostate cancer compared with BPH and normal prostate central gland. This was significantly (p < 0.01) reflected by lower mean citrate/[creatine+choline] peak area ratio and citrate/lipid peak area ratio observed for region of cancer (0.446 ± 0.063, 0.097 ± 0.030) compared with BPH (1.458 ± 0.107, 0.786 ± 0.162) and normal central gland (1.418 ± 0.129, 0.175 ± 0.011), respectively. These studies demonstrate the potential of citrate spectrum detected by an external-body surface coil as an in vivo marker for discriminating prostate cancer from BPH.     

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.     

Emerging spectroscopic techniques for prostate cancer diagnosis

ABSTRACT

Over the past several decades, large efforts have been made to diagnose and overcome prostate cancer. Among all screening methods, the measurement of prostate-specific antigen (PSA) threshold has been stood out and contributed to diagnose prostate cancer (PCa) in a large number of men. Nevertheless, the early detection of prostate carcinoma and its focal imaging is remaining crucial to diminish the elevated number of PCa-related deaths. Because of the multifocal behavior of PCa development, a whole gland ablation has been practiced during previous years. Furthermore, there is an evidence of the likelihood of high-risk PCa that proves once again the importance of early diagnosis and accurate staging of the disease. So far, numerous advanced spectroscopic methods with different approaches have been reported as the alternative tools to conventional techniques of PCa diagnosis and imaging. In this review, we introduce innovative emerging techniques utilizing spectroscopic methods such as photoluminescence, surface-enhanced Raman spectroscopy, and surface plasmon resonance to measure the ultralow level of PSA. In addition, we review novel and alternative approaches of diagnosis such as imaging methods through photoluminescence, magnetic resonance imaging, and positron emission tomography.     

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.     

Abnormal uterine cavity: differential diagnosis with MR imaging

The objective of the study was to assess the usefulness of magnetic resonance (MR) imaging in distinguishing malignant from benign conditions in patients with an abnormal uterine cavity. Fifty-four patients that were suspected of having abnormal uterine cavities were retrospectively evaluated by using MR imaging. The diagnosis of an abnormal uterine cavity included a thickened endometrium, and/or a endometrial mass, and/or a submucosal mass. Threshold values to classify the uterine cavity as abnormal on sagittal T₂-weighted images were >10 mm for premenopausal women and >5 mm for postmenopausal women. Malignancy was diagnosed when lesions invaded the myometrial/junctional zone, and/or lesion enhancement was lower than that of the adjacent myometrium. The results found that histology confirmed 18 malignant and 37 benign lesions. Twelve of 15 endometrial carcinomas and 3 malignant mixed mesodermal tumors (MMMT) were correctly characterized as malignant on enhanced T₁-weighted images; whereas 6 of 15 endometrial carcinomas and 3 MMMT were correctly characterized on T₂-weighted images. Thirty-four of 37 benign cases were correctly characterized as not malignant on enhanced T₁-weighted images. One of 14 submucosal leiomyomas, one endometrial stromal metaplasia, and one of ten pathologically normal endometria were misdiagnosed on enhanced T₁-weighted images but were correctly diagnosed on T₂-weighted images. The overall sensitivity, specificity, and accuracy for distinguishing malignant from benign central uterine masses were 83%, 92%, and 89% for enhanced T₁-weighted image, and 50%, 97%, and 82% for T₂-weighted image, respectively. We came to the conclusion that in diagnosing patients with abnormal uterine cavity, MR imaging may help differentiate malignant from benign disorders.     

Vibro-acoustography imaging of permanent prostate brachytherapy seeds in an excised human prostate - Preliminary results and technical feasibility

Objective:

The objective in this work is to investigate the feasibility of using a new imaging tool called vibro-acoustography (VA) as a means of permanent prostate brachytherapy (PPB) seed localization to facilitate post-implant dosimetry (PID).

Methods and materials:

Twelve OncoSeed (standard) and eleven EchoSeed (echogenic) dummy seeds were implanted in a human cadaver prostate. Seventeen seeds remained after radical retropubic prostatectomy. VA imaging was conducted on the prostate that was cast in a gel phantom and placed in a tank of degassed water. 2-D magnitude and phase VA image slices were obtained at different depths within the prostate showing location and orientation of the seeds.

Results:

VA demonstrates that twelve of seventeen (71%) seeds implanted were visible in the VA image, and the remainder were obscured by intra-prostatic calcifications. Moreover, it is shown here that VA is capable of imaging and locating PPB seeds within the prostate independent of seed orientation, and the resulting images are speckle free.

Conclusion:

The results presented in this research show that VA allows seed detection within a human prostate regardless of their orientation, as well as imaging intra-prostatic calcifications.     

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.     

Surgical and chemical castration induce differential histological response in prostate lobes of Mongolian gerbil

The present study describes the short-term alterations in the prostate ventral and dorsal lobe of the adult Mongolian gerbil, in response to two different androgen suppression approaches. Groups (n=6) of 16-week-old gerbils were maintained intact or subjected, either to the bilateral surgical castration 1 week previously or to daily subcutaneous injections of Flutamide (10mg/kg body weight) for 7 days. The main microscopic features of both prostate lobes in these groups were compared using conventional paraffin tissue sections, measurements of acinar epithelial height and stereological data of main gland components (acini, collagen fibers and fibromuscular stroma). Marked alterations were observed in the basement membrane of the ventral lobe after both surgical and chemical castration, such as an increase in thickness and collagen staining. A low degree of epithelial atrophy was detected in the dorsal lobe following both androgen suppression approaches in comparison with that found in the ventral lobe, indicating that this lobe is not so responsive to testosterone ablation induced by castration or Flutamide treatment, at least insofar as secretory activity is concerned. However, the dorsal lobe exhibited marked stromal modification, such as an increase in collagen fibers following castration and an increase in fibromuscular stroma following Flutamide-treatment. Thus, the histological and quantitative data indicates a differential short-term response of the prostate dorsal lobe to surgical castration and Flutamide therapy, suggesting the existence of lobe-specific mechanisms for stromal remodeling.     

The orientational glass transition in pentachloronitrobenzene: a study by differential scanning calorimetry and thermally stimulated currents

The orientational disorder that is a feature of the crystalline pentachloronitrobenzene above ∼−82 °C, can be frozen by cooling to produce an orientational glass. The number of degrees of freedom frozen on cooling, or released on heating, in this orientational glass transition is low, so that the heat capacity change associated with this transition is expected to be small. In the present work, we show that the calorimetric signature of this orientational glass transition is in fact very weak. Conversely, since the molecular motions associated with this relaxation drag strong dipoles, the technique of thermally stimulated depolarisation currents (TSDC) provides a very strong signature of this transition. The orientational glass transition in pentachloronitrobenzene was studied by TSDC and, from this study, it was shown that this orientational glass belongs to the class of very strong glasses in the fragility scale proposed by Angell.     

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.     

Aptamer-conjugated multi-walled carbon nanotubes as a new targeted ultrasound contrast agent for the diagnosis of prostate cancer

Early diagnosis is primarily important for the therapeutic and prognostic outcomes of malignancies including prostate cancer (PCa). However, the visuality and veracity of ultrasound imaging for the diagnosis and prognostic prediction of PCa remains poor at present. In this study, we developed a new nanoultrasound contrast agent by modifying multi-walled carbon nanotubes (MWCNTs) with polyethylene glycol (PEG) and anti-PSMA aptamer. The result showed that the modified MWCNTs offered better visuality and veracity and were able to target PCa cells more effectively as compared with the traditional contrast agent. The zeta potential was about ??38 mv. The length of this contrast agent was about 400 nm and the diameter of it was about 30 nm. The zeta potential, TEM, and FT-IR all proved the successful preparation of the agent. The vitro cytological study revealed good cell uptake and biocompatibility of the new contrast agent. The minimum detection concentration in vitro is 10 μg/ml. The earliest stage of the detection was under the parameters of frequency?=?6.0 MHz and medical index?=?0.06. Both in vitro and in vivo ultrasound imaging demonstrated that the new nanoultrasound contrast agent had a good development effect, distribution, and metabolism, and may prove to be a good targeted ultrasound contrast agent, especially for PCa.     

Cystic intracranial mass lesions: Possible role of in vivo MR spectroscopy in its differential diagnosis

Thirty-four patients showing cystic intracranial mass lesions on MR imaging were evaluated by in vivo proton MR spectroscopy (MRS) with the aim of detecting lesion-specific spectral patterns that may assist imaging in better tissue characterization. In vivo spectroscopy was performed using stimulated echo acquisition mode with echo times 20 m and 270 m in all, and spin echo with echo time 135 m in 11 patients. All primary neoplasms (intra-as well as extra-axial) showed choline (3.22 ppm) resonance along with lipid and/or lactate (1.3 ppm). It was not possible to grade cystic gliomas based on N-acetyl asparate-to-choline ratio. High-grade gliomas (n = 8) showed lipid/lactate and low-grade gliomas (n = 6) showed only lactate. Seven patients with brain abscess showed resonances only from acetate (1.92 ppm), lactate (1.3 ppm) and alanine (1.5 ppm). Two cases of metastatic adenocarcinoma showed only lipid/lactate. In 7 patients with epidermoid cyst, lactate along with an unassigned resonance at 1.8 ppm was observed and could be easily differentiated from arachnoid cyst (n = 2), which showed only minimal lactate. A case of cystic meningioma could be differentiated from cystic schowannoma by the presence of alanine in the former. It is concluded that MR imaging, when combined with in vivo MRS, may help to better characterize intracranial cystic mass lesions.     

Recurrent hepatocellular carcinoma versus radiation-induced hepatic injury: differential diagnosis with MR imaging

The objective of this study was to assess the value of MR imaging in the differentiation between a recurrent hepatocellular carcinoma (HCC) and a radiation-induced hepatic injury. Nine male patients with suspected recurrence after radiotherapy for HCC underwent T(2)-, T(1)-weighted imaging and Gd-DTPA enhanced dynamic studies. T(2) relaxation times, signal intensity ratios in T(1)-weighted images (WI) and the relative enhancement of the dynamic study were calculated. Recurrent tumors and the irradiated area showed similar image characteristics: hypointense in T(1)-WI and hyperintense in T(2)-WI. T(2) values and signal intensity ratios in the T(1)-WI were not significantly different. In the gadolinium-enhanced dynamic study, a recurrent HCC showed early enhancement, followed by a rapid washout. However, the irradiated liver parenchyma showed hyperintensity from an early phase, and contrast enhancement tended to be more prominent and prolonged at the end of the dynamic studies. The characteristic findings of the dynamic MR study enable us to distinguish between a recurrent HCC and a radiation-induced hepatic injury.     

Diffusion-weighted imaging of local recurrent prostate cancer after radiation therapy: comparison with 22-core three-dimensional prostate mapping biopsy

Accurate localization of local recurrence within the prostate gland is important to perform focal salvage therapy effectively with minimal complications. The purpose of this study was to evaluate the usefulness of diffusion-weighted imaging (DWI) in the detection and localization of prostate cancer recurrence in patients with biochemical failure after definitive radiation therapy using 22-core three-dimensional prostate mapping biopsy (3D-PMB) as a standard reference. Ten patients who underwent magnetic resonance imaging and 22-core 3D-PMB were retrospectively analyzed. For visual assessment of DWI, the prostate was divided into 22 regions corresponding to 3D-PMB. Two diagnostic radiologists determined the presence of abnormal high signal intensity in each region on DWI, and the results of DWI were compared with those of 3D-PMB. Of the 220 regions, 16 regions in six patients were positive for cancer on 3D-PMB, and 30 regions in six patients were judged as positive on DWI. On a patient-by-patient basis, sensitivity and specificity were 100% (6/6) and 100% (4/4), respectively. On a region-by-region basis, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 69% (11/16), 91% (185/204), 37% (11/30), 97% (185/190) and 89% (196/220), respectively. For discrepant localization between DWI and pathology, DWI-positive and pathology-positive regions tended to be adjacent to each other. In conclusion, DWI is a useful tool for the detection and localization of recurrent prostate cancer in patients with biochemical failure after radiation therapy and may be helpful in the planning of focal salvage therapy.     

Balanced differential phase-shift keying detector performance: an analytical study

A simple explanation of the observed approximately 3 dB advantage of differential phase-shift keying (DPSK) balanced detection over the intensity-modulated directly detected (IM-DD) type detection that can be easily used for system engineering purposes is presented. A Gaussian approximation is used to describe the tails of the detected noisy random signals leading to an analytical explanation of the observed approximately 3 dB advantage of DPSK balanced detection over the IM-DD type detection.     

Solution of singular two-point boundary value problems using differential transformation method

In this Letter, we implemented relatively new, exact series method of solution known as the differential transform method for solving singular two-point boundary value problems. Several illustrative examples are given to demonstrate the effectiveness of the present method.     

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.     

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.     

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.