Prostate cancer is the most common solid organ cancer in men, and the second most common cause of male cancer-related mortality. It has few effective therapies, and is difficult to diagnose accurately. Prostate-specific antigen (PSA), which is currently the most effective diagnostic tool available, cannot reliably discriminate between different pathologies, and in fact only around 30% of patients found to have elevated levels of PSA are subsequently confirmed to actually have prostate cancer. As such, there is a desperate need for more reliable diagnostic tools that will allow the early detection of prostate cancer so that the appropriate interventions can be applied. Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance spectroscopy (MRS) are 2 high throughput, noninvasive analytical procedures that have the potential to enable differentiation of prostate cancer from other pathologies using metabolomics, by focusing specifically on certain metabolites which are associated with the development of prostate cancer cells and its progression. The value that this type of approach has for the early detection, diagnosis, prognosis, and personalized treatment of prostate cancer is becoming increasingly apparent. Recent years have seen many promising developments in the fields of NMR spectroscopy and MRS, with improvements having been made to hardware as well as to techniques associated with the acquisition, processing, and analysis of related data. This review focuses firstly on proton NMR spectroscopy of blood serum, urine, and expressed prostatic secretions in vitro, and then on 1- and 2-dimensional proton MRS of the prostate in vivo. Major advances in these fields and methodological principles of data collection, acquisition, processing, and analysis are described along with some discussion of related challenges, before prospects that proton MRS has for future improvements to the clinical management of prostate cancer are considered.

Nuclear magnetic resonance spectroscopy of human body fluids and in vivo magnetic resonance spectroscopy: Potential role in the diagnosis and management of prostate cancer.

The aim of this study was to evaluate the diagnostic performance of the use of total choline signal-to-noise ratio (tCho SNR) criteria in MRS studies for benign/malignant discrimination of focal breast lesions. We conducted (1) a meta-analysis based on 10 studies including 480 malignant breast lesions and 312 benign breast lesions and (2) a subgroup meta-analysis of tCho SNR ≥ 2 as cutoff for malignancy based on 7 studies including 371 malignant breast lesions and 239 benign breast lesions. (1) The pooled sensitivity and specificity of proton MRS with tCho SNR were 0.74 (95 % CI 0.69–0.77) and 0.76 (95 % CI 0.71–0.81), respectively. The PLR and NLR were 3.67 (95 % CI 2.30–5.83) and 0.25 (95 % CI 0.14–0.42), respectively. From the fitted SROC, the AUC and Q* index were 0.89 and 0.82. Publication bias was present (t = 2.46, P = 0.039). (2) Meta-regression analysis suggested that neither threshold effect nor evaluated covariates including strength of field, pulse sequence, TR and TE were sources of heterogeneity (all P value >0.05). (3) Subgroup meta-analysis: The pooled sensitivity and specificity were 0.79 and 0.72, respectively. The PLR and NLR were 3.49 and 0.20, respectively. The AUC and Q* index were 0.92 and 0.85. The use of tCho SNR criteria in MRS studies was helpful for differentiation between malignant and benign breast lesions. However, pooled diagnostic measures might be overestimated due to publication bias. A tCho SNR ≥ 2 as cutoff for malignancy resulted in higher diagnostic accuracy.

1H-MRS evaluation of breast lesions by using total choline signal-to-noise ratio as an indicator of malignancy: a meta-analysis

1H Magnetic Resonance Spectroscopy Predicts Hepatocellular Carcinoma in a Subset of Patients With Liver Cirrhosis: A Randomized Trial.

The aim of this study is to perform a meta-analysis to evaluate the diagnostic performance of the in vivo post-contrast proton magnetic resonance spectroscopy (MRS) for benign/malignant discrimination of focal breast lesions. Sixteen studies with a total of 661 malignant breast lesions and 388 benign breast lesions were included. The pooled sensitivity and specificity of post-contrast 1H-MRS were 74 % (95 % confidence interval (CI) 70–77 %) and 78 % (95 % CI 73–82 %), respectively. The positive likelihood ratio (PLR) and the negative likelihood ratio (NLR) were 4.00 (95 % CI 2.74–5.84) and 0.25 (95 % CI 0.17–0.37), respectively. From the fitted summary receiver operating characteristics curve (SROC), the AUC and Q* index were 0.89 and 0.83. Publication bias was present (t = 2.43, P = 0.029). Meta-regression analysis suggested that neither threshold effect nor evaluated covariates including method of choline analysis, strength of field, pulse sequence, repetition time (TR), and time interval were sources of heterogeneity (all P values >0.05). In vivo post-contrast 1H-MRS was useful for differentiation between malignant and benign focal breast lesions. However, pooled diagnostic measures might be overestimated. The standardization of the acquisition protocol as well as the post-processing method for post-contrast proton MRS need to be established for the future study.

In vivo post-contrast 1H-MRS evaluation of malignant and benign breast lesions: a meta-analysis.

Liver cirrhosis (LC) can develop hepatocellular carcinoma (HCC). However, noninvasive early diagnosis of HCCs in the cirrhotic liver is still challenging. We aimed to quantify the hepatic metabolites in normal control (NC), cirrhotic liver without HCC, cirrhotic liver with HCC (CLH), and early-stage HCC groups using proton magnetic resonance spectroscopy (1H-MRS) with a long echo-time (TE) and to assess the potential association between the levels of hepatic metabolites in these four groups and aging and enzymatic activity. Thirty NCs, 30 viral hepatitis-induced LC patients without HCC, and 30 viral hepatitis-induced LC patients with HCC were included in this study. 1H-MRS measurements were performed on a localized voxel of the normal liver parenchyma (n = 30) from NCs, cirrhotic liver parenchyma (n = 30) from LC patients without HCC, and each of the cirrhotic liver parenchyma (n = 30) and HCC (n = 30) from the same patients in the CLH group. Generalized estimating equations were used to evaluate potential risk factors for changes in metabolite levels. Potential associations between metabolite levels and age and serum enzymatic activities were assessed by correlation analysis. The levels of lactate+triglyceride (Lac+TG) and choline (Cho) in HCC were significantly higher compared to those in LC and CLH. A potential risk factor for changes in the Lac+TG and Cho levels was age, specifically 60-80 years of age. In particular, the Lac+TG level was associated with a high odds ratio of HCC in males aged 60-80 years. The Lac+TG and Cho concentrations were positively correlated with lactate dehydrogenase and alkaline phosphatase activities, respectively. Our findings suggested that 1H-MRS measurement with a long TE was useful in quantifying hepatic Lac+TG and Cho levels, where higher Lac+TG and Cho levels were most likely associated with HCC-related metabolism in the viral hepatitis-induced cirrhotic liver. Further, the level of Lac+TG in HCC was highly correlated with older age and lactate dehydrogenase activity.

https://www.mdpi.com/2077-0383/9/3/765/pdf

Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study.

AIM: To investigate the normal hepatic magnetic resonance spectroscopy findings choline/lipid2 (Cho/Lip2) associated with age and body mass index (BMI).

METHODS: A total of 58 single-voxel proton spectra of the liver were acquired at 3.0 T using the eight-channel phased array abdominal coil as the receiver coil. Consecutive stacks of breath-hold spectra were acquired using the point resolved spectroscopy technique at a short echo time of 30 ms and a repetition time of 1500 ms. The spectra were processed with the SAGE software package. Areas and heights for metabolite resonance were obtained. Student’s t test for unpaired data was used for comparisons of shimming, Cho/Lip2, and lipid content.

RESULTS: There were significant negative correlations between the Cho/Lip2 peak height ratios and BMI (r = -0.615) and age (r = -0.398) (all P < 0.01). Compared with the high-BMI group, the low-BMI group was younger (39.1 ± 13.0 years vs 47.6 ± 8.5 years, t = -2.954, P = 0.005); had better water suppression (93.4% ± 1.4% vs 85.6% ± 11.6%, t = 2.741, P = 0.014); had higher Cho/Lip2 peak heights ratio (0.2 ± 0.14 vs 0.05 ± 0.04, t = 6.033, P < 0.000); and had lower lipid content (0.03 ± 0.08 vs 0.29 ± 0.31, t = -3.309, P = 0.004). Compared with the older group, the younger group had better shimming effects (17.1 ± 3.6 Hz vs 22.0 ± 6.8 Hz, t = -2.919, P = 0.008); higher Cho/Lip2 peak heights ratios (0.03 ± 0.05 vs 0.09 ± 0.12, t = 2.4, P = 0.020); and lower lipid content (0.05 ± 0.11 vs 0.23 ± 0.32, t = -2.337, P = 0.031). Compared with the low-choline peak group, the high-choline peak group had lower lipid content (0.005 ± 0.002 vs 0.13 ± 0.23, t = -3.796, P < 0.000); lower BMI (19.6 ± 2.4 vs 23.9 ± 3.0, t = -4.410, P < 0.000); and younger age (34.7 ± 10.0 years vs 43.2 ± 12.5 years, t = -2.088, P = 0.041).

CONCLUSION: Lipid accumulation could result from the increased fat in the body depending on age and BMI. Lipid can mask the resonance signal of choline.

3.0 T proton magnetic resonance spectroscopy of the liver: Quantification of choline

Purpose. To determine whether administration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) and whether placement of the outer volume saturation bands significantly affect shimming and water suppression on hepatic MR spectroscopic prescanning. Method. Region of interest (ROI) of 2 cm × 2 cm × 2 cm was carefully positioned in the region of the middle portion of the right hepatic lobe. 32 patients were examined before and after administration of Gd-DTPA with and without outer-volume saturation bands. Linewidths (Full-Width Half-Maximum (FWHM)) and water suppression were obtained. A paired t-test for comparison of means was used. Results. (1) The group with the outer volume saturation bands demonstrated slightly better water suppression effect than the group without outer volume saturation bands before administration. (2) The group with the outer volume saturation bands demonstrated better water suppression effect than the group without outer volume saturation bands after administration. (3) Both shimming and water suppression effectswere decreased on enhanced MR spectroscopic prescanning (all ). Conclusions. Placement of the outer volume saturation bands is helpful to improve water suppression both before and after contrast agent administration. Gd-DTPA exerts a slightly adverse effect (a statistically significant but clinically unimportant) on magnetic resonance spectroscopic prescanning at 3T.

/pdf/effects-of-contrast-agent-and-outer-volume-saturation-bands-3ifdj2pazc.pdf

Effects of contrast agent and outer volume saturation bands on water suppression and shimming of hepatic single-volume proton MR spectroscopy at 3.0T.

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3.0 T proton magnetic resonance spectroscopy of the liver: Quantification of choline

Effects of contrast agent and outer volume saturation bands on water suppression and shimming of hepatic single-volume proton MR spectroscopy at 3.0T.