Proton MR spectroscopy of prostatic tissue focused on the etection of spermine, a possible biomarker of malignant behavior in prostate cancer

To investigate whether polyamines may be valuable diagnostic and prognostic markers in prostate cancer, the presence of alyamines was studied in various human prostatic tissues using both proton magnetic resonance (MR) spectroscopy and righ-pressure liquid chromatography (HPLC). The HPLC results showed that normal and benign hyperplastic prostatic tissues re characterized by a high content of spermine. Spermine levels were reduced in tumor tissue, especially in prostatic carcinoma h metastases, and in xenografts of human prostatic carcinoma cells. These preliminary results indicate that spermine may be d as a biomarker for malignant behavior. The MR spectroscopy study showed that it is possible to detect spermine resonances prostatic biopsy material by one-dimensional and two-dimensional J-resolved MR spectroscopy at high field (600 MHz). ocalized one-dimensional in vitro MR spectra obtained at the clinical field strength of 1.5 T showed spermine signals in the region between 3.0 and 3.3 ppm. In in vivo MR spectra of the human prostate, however, these signals were obscured by esonances of choline (3.2 ppm) and creatine (3.0 ppm).     

Quantitative proton MRS assessment of citrate heterogeneity in normal prostate

Water-suppressed proton spectra of the two major anatomical regions of the normal prostate were acquired with a commercial phased-array multicoil. The spectra demonstrated excellent signal-to-noise ratio and spectral resolution allowing identification of peaks from choline, creatine, and amino acids, as well as a major peak from citrate. Quantification of the citrate peak using tissue water as an internal concentration reference revealed a marked variability among different volunteers. In each case, citrate was consistently twofold to threefold greater in the peripheral zone than in the central gland. The results demonstrate heterogeneity of citrate within the prostate and suggest significant differences in the cytology and hormonal control of citrate synthesis among individuals.     

MR imaging of the prostate in clinical practice

Magnetic resonance imaging (MRI) is the imaging tool of choice in the evaluation of prostate cancer. The main applications of MR imaging in the management of prostate cancer are: (1) to guide targeted biopsy when prostate cancer is clinically suspected and previous ultrasound-guided biopsy results are negative; (2) to localize and stage prostate cancer and provide a roadmap for treatment planning; and (3) to detect residual or locally recurrent cancer after treatment. Other MR techniques such as proton MR spectroscopic imaging (MRSI), diffusion-weighted imaging (DWI), and contrast-enhanced MRI (CE-MRI) complement conventional MR imaging by providing metabolic and functional information that can improve the accuracy of prostate cancer detection and characterization. In everyday clinical practice, and to account for patient comfort, MR imaging studies are limited to 1 h. To obtain consistently high-quality images, a well-designed protocol is necessary. Routine MR imaging can be supplemented by other MR techniques such as MRSI, DWI or CE-MRI depending on the expertise available and the clinical questions that need to be answered. This review summarizes the role of MR imaging in the management of prostate cancer and describes practical approaches to implementing anatomic, metabolic and functional MR imaging techniques in the clinic.     

Cervical cancer tissue characterized by high-resolution magic angle spinning MR spectroscopy

Objective: In recent years, high-resolution magic angle spinning (HR MAS) has provided the opportunity to explore detailed biochemical composition of intact tissue. Previous studies of intact cervical biopsies with high-resolution magnetic resonance spectroscopy (MRS) have correlated well with histopathology. Lactate level in cervical cancer tissue has been found to correlate to metastatic spread. The purpose of this study was to explore the potential of the HR MAS technique as a tool for chemical characterization of cervical cancer tissue. Materials and methods: Tissue samples from the cervix were collected after hysterectomy from patients with cervical cancer (n=8) and patients with nonmalignant disease (n=8). The tissue specimens were analyzed using HR MAS MR spectroscopy combined with principal component analysis (PCA). Results: The resulting spectra showed resolution comparable with high-resolution MR spectra of extracts. Multivariate analysis confirmed that MAS spectra classified according to patient diagnosis. Conclusion: Malignant tissue of the cervix differed from nonmalignant tissue with regard to higher levels of cholines and amino acid residues and lower levels of glucose.     

Fitting interrelated datasets: metabolite diffusion and general lineshapes

Objective

Simultaneous modeling of true 2-D spectroscopy data, or more generally, interrelated spectral datasets has been described previously and is useful for quantitative magnetic resonance spectroscopy applications. In this study, a combined method of reference-lineshape enhanced model fitting and two-dimensional prior-knowledge fitting for the case of diffusion weighted MR spectroscopy is presented.

Materials and methods

Time-dependent field distortions determined from a water reference are applied to the spectral bases used in linear-combination modeling of interrelated spectra. This was implemented together with a simultaneous spectral and diffusion model fitting in the previously described Fitting Tool for Arrays of Interrelated Datasets (FiTAID), where prior knowledge conditions and restraints can be enforced in two dimensions.

Results

The benefit in terms of increased accuracy and precision of parameters is illustrated with examples from Monte Carlo simulations, in vitro and in vivo human brain scans for one- and two-dimensional datasets from 2-D separation, inversion recovery and diffusion-weighted spectroscopy (DWS). For DWS, it was found that acquisitions could be substantially shortened.

Conclusion

It is shown that inclusion of a measured lineshape into modeling of interrelated MR spectra is beneficial and can be combined also with simultaneous spectral and diffusion modeling.

     

Benign prostate hyperplasia: evaluation of treatment response with DCE MRI

Benign prostate hyperplasia (BPH) is a major disease and its non-surgical therapy a major area of interest. The purpose of this study was to establish perfusion parameters in beagles with BPH using dynamic contrast-enhanced (DCE) MRI and to investigate changes due to the effects of finasteride treatment. Twelve male beagles (mean age 4.4±0.9,years) were divided into a control and treatment group that received a daily dose of 1 mg/kg finasteride. DCE MRI was carried out in a clinical scanner using a 3D spoiled gradient echo sequence prior to and during treatment. 0.2 mmol/kg contrast agent (gadoteridol) was administered with an injection rate of 0.2 ml/s followed by a 15 ml flush of saline. Contrast enhancement was evaluated by pharmacokinetic mapping of a two-compartment model with colour overlay images in addition to regional ROI analysis. Quantitative parameters were defined by the amplitude of contrast enhancement A, the exchange rate k_ep and the time to maximum signal enhancement. Dynamic contrast-enhanced MRI investigations of the prostate revealed two distinct zones, an inner, periurethral zone and an outer, parenchymal zone. The periurethral zone is highly vascularized, whereas the parenchymal zone is moderately vascularized when compared to other parenchymal organs. During treatment, in the parenchymal zone the intensity of enhancement (amplitude A) and the time to maximum signal enhancement increased, while the exchange rate k_ep decreased. Dynamic contrast-enhanced MRI of BPH reveals distinct differences between individual zones within the prostate. Moreover, changes during successful treatment suggest increased blood volume per volume of tissue and decreased vessel leakiness.     

High resolution magic angle spinning NMR spectroscopy for metabolic assessment of cancer presence and Gleason score in human prostate needle biopsies

Objectives  Histopathology of prostate needle biopsies (PNBs) is an important part in the diagnosis, prognosis and treatment evaluation of prostate cancer. The determination of metabolite levels in the same biopsies may have additional clinical value. Here, we demonstrate the use of non-destructive high resolution magic angle spinning (HRMAS) proton NMR Spectroscopy for the assessment of metabolic profiles of prostate tissue in PNBs as commonly obtained in standard clinical practice. Materials and methods  PNBs that were taken routinely from 48 patients suspected of having prostate cancer were subjected to HRMAS proton NMR spectroscopy. Subsequent histopathology of the same biopsies classified the tissue either as cancer (n = 10) or benign (n = 30). Results  Some practical aspects of this assessment were evaluated, such as typical spectral contamination caused by the PNB procedure. Significant metabolic differences were found between malignant and benign tissue using a small set of ratio’s involving signals of choline compounds, citrate and lactate. Moreover, significant correlations were observed between choline, total choline, and citrate over creatine signal ratios and the Gleason scores of tumor in PNBs and of tumor in the whole prostate. Conclusion  This preliminary study indicates that HRMAS NMR of routinely obtained PNBs can provide detailed metabolic information of intact prostate tissue with clinical relevance. Albert Verhofstad died before publication of this article.     

Role of magnetic resonance methods in the evaluation of prostate cancer: an Indian perspective

The challenges in detection, localization, and staging of prostate cancer have prompted the investigation of the role of various magnetic resonance (MR) methodologies in a large cohort of men prior to biopsy. The identification of suspicious areas of malignancy was carried out using magnetic resonance imaging (MRI), magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI). Our data shows that apparent diffusion coefficient (ADC) may be a reliable marker to differentiate normal, benign, and malignant prostate tissues similar to the metabolite ratio. Also, the combined use of MRSI and DWI improves the diagnosis of prostate cancer. In this review, we present our experience on the use of MRI, MRSI and DWI methods in the assessment of prostate cancer in Indian men. Further, analysis of the comparison of the ADC and the metabolite ratio values reported in the literature across various patient populations are presented. An erratum to this article can be found at     

Multiproject–multicenter evaluation of automatic brain tumor classification by magnetic resonance spectroscopy

Justification  Automatic brain tumor classification by MRS has been under development for more than a decade. Nonetheless, to our knowledge, there are no published evaluations of predictive models with unseen cases that are subsequently acquired in different centers. The multicenter eTUMOUR project (2004–2009), which builds upon previous expertise from the INTERPRET project (2000–2002) has allowed such an evaluation to take place. Materials and Methods  A total of 253 pairwise classifiers for glioblastoma, meningioma, metastasis, and low-grade glial diagnosis were inferred based on 211 SV short TE INTERPRET MR spectra obtained at 1.5 T (PRESS or STEAM, 20–32 ms) and automatically pre-processed. Afterwards, the classifiers were tested with 97 spectra, which were subsequently compiled during eTUMOUR. Results  In our results based on subsequently acquired spectra, accuracies of around 90% were achieved for most of the pairwise discrimination problems. The exception was for the glioblastoma versus metastasis discrimination, which was below 78%. A more clear definition of metastases may be obtained by other approaches, such as MRSI + MRI. Conclusions  The prediction of the tumor type of in-vivo MRS is possible using classifiers developed from previously acquired data, in different hospitals with different instrumentation under the same acquisition protocols. This methodology may find application for assisting in the diagnosis of new brain tumor cases and for the quality control of multicenter MRS databases.     

Monitoring and correcting spatio-temporal variations of the MR scanner’s static magnetic field

The homogeneity and stability of the static magnetic field are of paramount importance to the accuracy of MR procedures that are sensitive to phase errors and magnetic field inhomogeneity. It is shown that intense gradient utilization in clinical horizontal-bore superconducting MR scanners of three different vendors results in main magnetic fields that vary on a long time scale both spatially and temporally by amounts of order 0.8–2.5 ppm. The observed spatial changes have linear and quadratic variations that are strongest along the z direction. It is shown that the effect of such variations is of sufficient magnitude to completely obfuscate thermal phase shifts measured by proton-resonance frequency-shift MR thermometry and certainly affect accuracy. In addition, field variations cause signal loss and line-broadening in MR spectroscopy, as exemplified by a fourfold line-broadening of metabolites over the course of a 45 min human brain study. The field variations are consistent with resistive heating of the magnet structures. It is concluded that correction strategies are required to compensate for these spatial and temporal field drifts for phase-sensitive MR protocols. It is demonstrated that serial field mapping and phased difference imaging correction protocols can substantially compensate for the drift effects observed in the MR thermometry and spectroscopy experiments.     

FID modulus: a simple and efficient technique to phase and align MR spectra

Object

The post-processing of MR spectroscopic data requires several steps more or less easy to automate, including the phase correction and the chemical shift assignment. First, since the absolute phase is unknown, one of the difficulties the MR spectroscopist has to face is the determination of the correct phase correction. When only a few spectra have to be processed, this is usually performed manually. However, this correction needs to be automated as soon as a large number of spectra is involved, like in the case of phase coherent averaging or when the signals collected with phased array coils have to be combined. A second post-processing requirement is the frequency axis assignment. In standard mono-voxel MR spectroscopy, this can also be easily performed manually, by simply assigning a frequency value to a well-known resonance (e.g. the water or NAA resonance in the case of brain spectroscopy). However, when the correction of a frequency shift is required before averaging a large amount of spectra (due to B ₀ spatial inhomogeneities in chemical shift imaging, or resulting from motion for example), this post-processing definitely needs to be performed automatically.

Materials and methods

Zero-order phase and frequency shift of a MR spectrum are linked respectively to zero-order and first-order phase variations in the corresponding free induction decay (FID) signal. One of the simplest ways to remove the phase component of a signal is to calculate the modulus of this signal: this approach is the basis of the correction technique presented here.

Results

We show that selecting the modulus of the FID allows, under certain conditions that are detailed, to automatically phase correct and frequency align the spectra. This correction technique can be for example applied to the summation of signals acquired from combined phased array coils, to phase coherent averaging and to B ₀ shift correction.

Conclusion

We demonstrate that working on the modulus of the FID signal is a simple and efficient way to both phase correct and frequency align MR spectra automatically. This approach is particularly well suited to brain proton MR spectroscopy.     

Compatibility between 3T 1H SV-MRS data and automatic brain tumour diagnosis support systems based on databases of 1.5T 1H SV-MRS spectra

Object

This study demonstrates that 3T SV-MRS data can be used with the currently available automatic brain tumour diagnostic classifiers which were trained on databases of 1.5T spectra. This will allow the existing large databases of 1.5T MRS data to be used for diagnostic classification of 3T spectra, and perhaps also the combination of 1.5T and 3T databases.

Materials and methods

Brain tumour classifiers trained with 154 1.5T spectra to discriminate among high grade malignant tumours and common grade II glial tumours were evaluated with a subsequently-acquired set of 155 1.5T and 37 3T spectra. A similarity study between spectra and main brain tumour metabolite ratios for both field strengths (1.5T and 3T) was also performed.

Results

Our results showed that classifiers trained with 1.5T samples had similar accuracy for both test datasets (0.87 ± 0.03 for 1.5T and 0.88 ± 0.03 for 3.0T). Moreover, non-significant differences were observed with most metabolite ratios and spectral patterns.

Conclusion

These results encourage the use of existing classifiers based on 1.5T datasets for diagnosis with 3T ¹H SV-MRS. The large 1.5T databases compiled throughout many years and the prediction models based on 1.5T acquisitions can therefore continue to be used with data from the new 3T instruments.     

Prediction of pathological tumor volume in clinically localized prostate cancer: value of endorectal coil magnetic resonance imaging

The purpose of this study was to determine whether endorectal coil magnetic resonance imaging (MRI) enables accurate assessment of pathologic tumor volume in patients with clinically localized prostate carcinoma. Twenty-four patients with biopsy-proved prostate carcinoma underwent MRI at 0.5 T before radical prostatectomy. Tumor volumes were determined independently on axial fast-spin-echo (SE) T₂-weighted MR images and whole-mount pathology slides of the surgical specimens. At pathology, tumor volumes ranged from 0.17 to 9.42 cm³ (mean±SD, 3.11±2.99 cm³). A strong correlation (r=.944) was found between measurements of tumor volume based on MR images and pathological specimens. The error was less than 0.5 cm³ in 14 cases, in the range of 0.5–1 cm³ in 7 cases, and more than 1 cm³ in 3 cases. By using an MR tumor volume of 2 cm³ as cutoff value, extracapsular tumor spread could be predicted with a sensitivity of 81.2%, a specificity of 100%, and an accuracy of 87.5%. Tumor volume determinations based on MR images seem to be accurate enough to be helpful in clinical decision-making.     

Intraoperative application of optical spectroscopy in the presenceof blood

A simple but effective method of spectral processing was developed to minimize or remove the effects of the presence of superficial blood on tissue optical spectra and, hence, enhance the performance of optical-spectroscopic-based in vivo tissue diagnosis and surgical guidance. This spectral-processing algorithm was developed using the principles of absorption-induced light attenuation wherein the ratio of fluorescence intensity (F) and the hth power of diffuse reflectance intensity (Rd) at a given emission wavelength λ_m is immune to spectral distortions induced by the presence of blood on the tissue surface. Here, the exponent h is determined by the absorption coefficients of whole blood at the excitation and emission wavelengths. The theoretical basis of this spectral processing was verified using simulations and was experimentally validated. Furthermore, the optical spectra of brain tissues collected in vivo was processed using this algorithm to evaluate its impact on brain tissue differentiation using combined fluorescence and diffuse reflectance spectroscopy. Based on the simulation, as well as experimental results, it was observed that using F/Rd^h h can effectively reduce or remove spectral distortions induced by superficial blood contamination on tissue optical spectra. Thus, optical spectroscopy can also be used intraoperatively for applications such as surgical guidance of tumor resection     

1H spectroscopic imaging of acute head injury—evidence of diffuse axonal injury

Using single slice two-dimensional spectroscopic imaging (SI), nine acute head injury patients and six controls have been successfully scanned. The problems presented by the need for ITU monitoring of these patients during MR scanning was overcome using MR compatible monitoring equipment. In previous studies of head injury which used proton spectroscopy, single voxel localisation procedures have meant that the spatial extent of the spectral data has been limited. With spectral data from a whole axial slice, we have been able to identify NAA abnormalities in regions remote to any T2 visible lesions This suggests that SI (of NAA in particular) will be useful for the diagnosis of diffuse axonal injury.     

<Superscript>1</Superscript>H MR spectroscopy as a diagnostic tool for cerebral creatine deficiency

Objective  Total creatine (tCr) constitutes one of the most prominent signals in human brain MR spectra. A significant decrease in the tCr signal indicates a severe disorder of creatine metabolism. We describe the potential of ¹H MR spectroscopy in differential diagnosis of creatine transporter (SLC6A8) deficiency syndrome. Materials and methods  Two siblings, a 7-year-old female presenting with mild psychomotor delay, and a 5-year-old male with severe psychomotor retardation, epilepsy and autistic spectrum of problems including speech delay, underwent MR examination because of suspected creatine deficiency. After the MRI examination, ¹H MR spectroscopy using the CSI technique was performed. Results  Metabolic images of N-acetylaspartate, tCr and choline concentrations showed a very low tCr signal in the male, which was approximately three times lower than in his sister (male/female/controls: tCr = 1.6/4.6/7.5 mM). Despite creatine supplementation, no improvement in clinical status and tCr concentration in the MR spectra of the male was observed and diagnosis of SLC6A8 deficiency was proposed. Sequence analysis of the SLC6A8 gene revealed a novel pathogenic frameshift mutation c.219delC; p.Asn74ThrfsX23, hemizygous in the male and heterozygous in the female. Conclusions  The diagnosis of X-linked mental retardation caused by the SLC6A8 deficiency can be independently established by ¹H MR spectroscopy.     

电能质量扰动在线辨识装置

设计了一种具有电能质量(PQ)扰动实时在线检测与分类功能的电能质量分析装置.该装置基于DSP和FPGA平台,实现了信号的采集、处理和显示.在算法上由于人工神经网络、专家系统、模糊逻辑、支持向量机等分类器过于复杂,故采用一种简单、高效的PO扰动分类和量化方法,即基于规则基的决策树RBDT(Rule-Based Decision Tree)模式识别方法,同时提取5个典型的PQ扰动时频特征量作为决策树的输入量,实现了9种典型PQ扰动的辨识.通过算法仿真及硬件平台验证,结果表明可以满足对PQ扰动分类的精度和实时性的要求.     

Influence of pulse angle variations onstimulated echo acquisition mode proton nuclear magnetic resonance spectra of AB spin systems: theory and experiments with citrate

The influence of pulse angle variations in the localization sequence stimulated echo acquisition mode (STEAM) on the signal of strongly coupled AB spin systems has been examined. Experimental¹H nuclear magnetic resonance (NMR) spectra of citrate were recorded on a 1.5 T whole-body imager. Theoretically calculated spectra were generated, with good correlation to experimental results. The dependence of the signal intensity on sequence timing and pulse angles was calculated analytically. For longer sequence timings, the ratio of the signal intensity from citrate to the signal intensity from uncoupled nuclei depends strongly on the applied flip angles. The shape of spectra also changes with varying flip angles. These effects are clearly less pronounced for STEAM than for point resolved spectroscopy (PRESS). The results have to be considered for quantitative measurements of citrate in spectroscopic investigations as, e.g. of prostate neoplasms.     

Two-dimensional MR spectroscopy of healthy and cancerous prostates in vivo

Objectives  A major goal of this article is to summarize the current status of evaluating prostate metabolites non-invasively using spatially resolved two-dimensional (2D) MR Spectroscopy (MRS). Materials and Methods  Due to various technical challenges, the spatially resolved versions of 2D MRS techniques are currently going through the developmental stage. During the last decade, four different versions of 2D MRS sequences have been successfully implemented on 3T and 1.5T MRI scanners manufactured by three different vendors. These sequences include half and maximum echo sampled J-resolved spectroscopy (JPRESS), S-PRESS and L-COSY, which are single volume localizing sequences, and the multi-voxel based JPRESS sequence. Results  Even though greater than 1ml voxels have been used, preliminary evaluations of 2D JPRESS, S-PRESS and L-COSY sequences have demonstrated unambiguous detection of citrate, creatine, choline, spermine and more metabolites in human prostates. ProFIT-based quantitation of JPRESS and L-COSY data clearly shows the superiority of 2D MRS over conventional one-dimensional (1D) MRS and more than six metabolites have been successfully quantified. These sequences have been evaluated in a small group of prostate pathologies and pilot investigations using these sequences show promising results in prostate pathologies. Conclusion  Implementation of the state-of-the-art 2D MRS techniques and preliminary evaluation in prostate pathologies are discussed in this review. Even though these techniques are going through developmental and early testing phases, it is evident that 2D MRS can be easily added on to any clinical Magnetic Resonance Imaging (MRI) protocol to non-invasively record the biochemical contents of the prostate.