Evaluation of five protocols for quantification of two-dimensional MR spectroscopic images

Five protocols were tested for quantification onin vivo two-dimensional spectroscopic imaging datasets. The datasets are duplo measurements from three individuals. The peaks forN-acetyl aspartate, creatines, and cholines were quantified. The first of the protocols is conventional integration of a selected interval around the peak. The others are various implementations of a Gauss-Newton-based least-squares time-domain fitting algorithm. Fitting a half-echo (free-induction decay curve, FID) to a full echo was compared; this was combined with or without filtering out the water signal using the Lanczos-Hankel singular-value decomposition (LHSVD). It appears that conventional integration yields consistent and accurate results in comparison to the fitting methods. The combination of LHSVD and echo fitting performs equally well; advantages and disadvantages are discussed. The protocols using FID fitting perform poorly with these experimental datasets.     

7Li 2D CSI of human brain on a clinical scanner

Lithium salts have been widely used in the treatment of mood disorders, but the mechanism of action is still not clear. In this work, a methodology for two-dimensional Lithium-7 imaging on clinical systems is presented. The data were acquired using a phosphorus volume head coil that was re-tuned for the Lithium-7 frequency. A spectroscopic sequence was used to acquire the free induction decay (FID) after volume excitation using a hard pulse. The results obtained on the head of patients undergoing lithium treatment (n = 7, 0.6 mEq/1 average serum level) demonstrate that images of adequate signal to noise ratio (100:1) can be obtained in acceptable imaging times (55 min) using the proposed methodology. The distribution of ’’Li appears uniform in the brains of the patients studied.     

<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.     

Towards 1H-MRSI of the human brain at 7T with slice-selective adiabatic refocusing pulses

Objective To explore the possibilities of proton spectroscopic imaging (¹H-MRSI) of the human brain at 7 Tesla with adiabatic refocusing pulses. Materials and methods A combination of conventional slice selective excitation and two pairs of slice selective adiabatic refocusing pulses (semi-LASER) results in the formation of an echo from a localized volume. Depending on the used radio frequency (rf) coil efficiency and available rf power, the duration of the adiabatic full passage pulses (AFPs) is adapted to enable echo times down to 50 ms (head coil) or 30 ms (local surface coil). Results An AFP duration of 5 ms with a corresponding bandwidth of 5.1 kHz resulted in a chemical shift displacement error of 23% over 3.8 ppm at 7T. Using a local surface coil and an echo time down to 30 ms, we detected not only the three main metabolites (NAA, Cr and Cho), but also coupled signals from myo-inositol and glutamate/glutamine in spectra from 0.14 cc voxels with linewidths down to 10 Hz in 10 min measurement time. Conclusions The semi-LASER pulse sequence enables ¹H-MRSI of the human brain at 7T for larger parts of the brain as well as small localized areas with both a high spectral and spatial resolution. Part of this work has been presented at the ISMRM-ESMRMB joint meeting in 2007 in Berlin, Germany, abstract number 43.     

Regional metabolite levels of the normal posterior fossa studied by proton chemical shift imaging

MR spectroscopy of the posterior fossa is pitted with numerous technical difficulties. It is, however, of great clinical interest in the study of the degenerative diseases and tumors of this area. We have developed a method to perform 2D CSI of this area, by using a sagittal slice and a careful positioning of outer volume saturation. We performed this acquisition in 30 healthy volunteers to determine the normal metabolic ratios in five voxels of this area (mesencephalon. pons. medulla oblongata, vermis, cerebellar white matter). The main technical difficulty was magnetic field inhomogeneity in the lower brainstem generated by dental alloys. However, 88% of the voxels were of sufficient quality to be analyzed. The statistically significant regional variations were a higher NAA/Cr ratio in the pons than in the medulla oblongata, higher Cho/Cr in the pons than in the mesencephalon and higher Cho/ Cr in the cerebellar white matter than in the vermis. We conclude that 2D CSI of the brainstem, although technically delicate can be performed in most patients.     

Chronic liver disease: relaxometry in the brain after liver transplantation

Relaxometry revealed changes in the basal ganglia in T₁ and T₂ relaxation times due to liver disease. Manganese is probably responsible for T₁ and T₂ shortening (as the concentration is known to be higher in both the liver and blood due to hepatic cirrhosis). The aim of this study was to follow possible recovery after liver transplantation by MR relaxometry. Together with a group of 20 healthy volunteers we scanned 53 patients before and after liver transplantation (some of them repeatedly). Both T₁ and T₂ values were evaluated in the basal ganglia, thalamus, and frontal white matter. T₁, relaxation timewas shortened by approx. 20–25% compared to the control group, probably the result of manganese deposition in the brain caused by hepatic cirrhosis. After liver transplantation the relaxation time recovered gradually with almost normal values reached approx. 2 years after surgery. T₁, recovery was observed in all evaluated structures. Similar results were observed with T₂ relaxation in the basal ganglia and thalamus. In the white matter T₂ remained low even 2 years after surgery.     

Mechanisms of31P relaxation in phosphorus metabolites

Measurements have been made of the longitudinal relaxation timeT ₁ of³¹P for the individual resonances of the metabolites AMP, ADP, ATP, P_ir and PCr (phosphocreatine) in H₂O and D₂O solutions from 5 to 60°C at various concentrations and at frequencies of 40 MHz (2.3 T) and 120 MHz (7 T). The contributions of dipolar, chemical shift anisotropy, and spin-rotation mechanisms have been separated, and activation parameters of the underlying molecular reorientations have been determined.     

T2-weighted breathold imaging of the liver: a quantitative and qualitative comparison of fast spin echo and half Fourier single shot fast spin echo imaging

The imaging characteristics of two EPI-hybrid breath-hold sequences, T2-weighted fast spin-echo [FSE, effective echo time (TE_eff) 138ms] and half Fourier single shot turbo spin-echo (HASTE, TE_eff 60 ms), were compared in hepatic imaging. A total of 111 patients with suspected hepatic disease were studied at 1.5 Tesla using a body phase-array coil. The signal-to-noise (S/N) and contrast-to-noise (C/N) ratios for organs and lesions were calculated and quantitatively compared. Organ delineation, visualization of anatomical structures and pathological lesions, artifacts, and total image quality were qualitatively assessed and statistically compared. The final diagnoses were metastases from colorectal, breast, and pancreatic cancer in 23/111, hepatocellular carcinoma in 15/111, cysts in 19/111, hemangiomas in 9/111, several other lesions in 7/111, and no lesions in 38/111 of the cases. A total of 139 lesion in 73% of the patients were seen while 85% of the lesions were at least 1.5 cm in size. Regarding S/Ns HASTE was significantly (P<0.03) superior to FSE with only minor (P>0.05) differences in C/Ns between the two sequences for anatomical and pathological structures. HASTE demonstrated in almost all (97.3%) of the cases no artifacts, while on fast SE imaging moderate to minor artifacts were present in 23.5–51.7% of the cases. The overall image quality and diagnostic confidence was rated significantly higher (good 43.2%, excellent 53.2%) for HASTE than for fast SE imaging (good 44.8%, excellent 17.6%). Providing comparable C/Ns for anatomical and pathological structures, breatheld HASTE imaging proved to be superior to fast SE in T2-weighted imaging of the upper abdomen regarding general image quality, and, with adequate technical prerequisites, may be a suitable substitute of fast T2-imaging techniques.     

Quantitative in vivo 1H spectroscopic imaging of metabolites in the early postnatal mouse brain at 17.6 T

Object  Early postnatal brain maturation is closely connected to local changes of metabolite levels. Spatially resolved in vivo ¹H NMR spectroscopic imaging is applied to follow absolute changes of brain metabolites in early postnatal mouse brain. Materials and methods  A short echo time semi LASER (localization by adiabatic selective refocusing) chemical shift imaging (CSI) sequence incorporating weighted k-space averaging was implemented at high magnetic field (17.6 T). In vivo measurements were carried out on postnatal days 5, 8, 12, 16, and 20. In vivo relaxation times T ₁ and T ₂ were measured using variable repetition times or a CPMG sequence, respectively, combined with LASER single voxel localization. Results  Spectra were obtained with a spatial resolution of (1 × 1) mm² in a 1.5 mm slice as early as postnatal day 5. Maturational changes of absolute metabolite concentrations of major metabolites were calculated in four different brain regions. A significant increase of N-acetylaspartate (NAA), total creatine (tCr), and glutamate/glutamine (Glx) concentration was paralleled by a decrease of taurine (Tau) concentration with age (P < 0.05). Differences between brain regions were found for NAA, tCr, and Tau (P < 0.05). Furthermore, in vivo T ₁ and T ₂ of the four major brain metabolites in adult mice are reported. Conclusion  The implemented semi LASER CSI sequence allows following regional changes of metabolite levels. It is suitable for investigation of local differences in brain metabolism and development.     

Quantification of metabolites from single-voxelin vivo 1H NMR data of normal human brain by means of time-domain data analysis

We present here a combination of time-domain signal analysis procedures for quantification of human brainin vivo ¹H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for theN-acetylaspartate, creatine, and choline-containing compounds were 11.4±1.0,6.5±0.5, and 1.7±0.2 mmol kg^–1 wet weight, respectively. The time-domain analyses ofin vivo ¹H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.     

Serial 1H-MRS in relapsing-remitting multiple sclerosis: effects of interferon-beta therapy on absolute metabolite concentrations

To assess the applicability of magnetic resonance spectroscopy (MRS) for long-term follow-up of neurological diseases a longitudinal 1H-MRS study at 3 T was carried out on ten patients having relapsing-remitting multiple sclerosis (MS) who, after baseline examination, received interferon-β (IFN) lb. At 8–20 examinations within up to 34 months absolute concentrations ofN-acetylaspartate (NAA), total creatine (tG), and choline-containing compounds (tCho) were determined in a large non-enhancing lesion and contralateral normal appearing white matter (NAWM). MR spectra were analyzed using a novel time domain-frequency domain method including non-parametric background characterization. For comparison at baseline, ten healthy controls were examined. The concentrations of tCho and tCr were found to be higher in MS brain than in control brain. Besides a non-significantly lower NAA concentration in lesions there were no concentration differences between lesions and NAWM. Over the follow-up period the measured metabolite concentrations exhibited a high variability. Most concentrations remained within this scatter, and statistical tests revealed significant fluctuations in the levels of metabolites in one case only. This stability of the metabolite concentrations over time might result from IFN therapy as for the spontaneous course of relapsing-remitting MS decreasing metabolite (NAA/tCr) ratios have been reported. The results further suggest that future treatment trials intending to use metabolite concentrations as a secondary outcome indicator use even longer observation periods and, besides group analysis of large cohorts, investigate the time behavior of selected single cases. The biochemical abnormalities found in NAWM emphasize the importance of analyzing both lesion and NAWM.     

Functional MR with use of FLASH sequences in the evaluation of the phono-articulatory tract

The aims of this study are to determine visualization of normal phonation structures with the use of MR fast sequences and anatomical reference indices which can be used in evaluating upper resonator pathologies. A total of 12 normal subjects were studied, a 1 T system, a volumetric receiving head and neck coil and FLASH sequences for one sagittal and two coronal scans. Each subject was instructed to take a deep breath and then to produce the vowel sounds for the entire duration of the scan. The movement of the following anatomical structures were considered: lips, tongue, soft palate, pharynx and epiglottis. For each subject sagittal scans were used to measure the minimal palate-tongue distance (p−t), the minimal anterio-posterior diameter of the mesopharynx (mp), and the epiglottis excursion angle (ep) with respect to the plane determined by the false vocal cords. Our results were compared with a diagrammed representation of tongue movements (vocal trapezium). This study underlines the validity of MR imaging techniques in the study of the phono-articulatory tract. because MR provided good detail of the phono-articulatory structures enabling an overall functional evaluation. MR would appear useful in evaluating defects in the velum and palate, in staging of oropharyngeal neoplasms and in surgical reconstructions of the tongue.     

Absolute quantification of high energy phosphate metabolites in normal, hypertrophied and failing human myocardium

2. Conclusion For definitive conclusions, larger numbers of patients will have to be studied, but our preliminary results indicate that (1) ATP levels decline in heart failure but not in left ventricular hypertrophy and (2) phosphocreatine/ATP ratios underestimate the true changes in myocardial high-energy phosphate concentrations in chronically injured human myocardium.     

<Superscript>1</Superscript>H-MRS of brain metabolites in migraine without aura: absolute quantification using the phantom replacement technique

Objective   

Several studies have demonstrated differences in migraine patients when performing ¹H-MRS; however, no studies have performed ¹H-MRS in migraine without aura (MwoA), the most common migraine subtype. The aim of this ¹H-MRS study was to elucidate whether any differences could be found between MwoA patients and controls by performing absolute quantification.     

Indirect evidence for the potential ability of magnetic resonance imaging to evaluate the myocardial iron content in patients with transfusional iron overload

The purpose of this study was to evaluate the potential ability of magnetic resonance imaging (MRI) for evaluation of myocardial iron deposits. The applied MRI technique has earlier been validated for quantitative determination of the liver iron concentration. The method involves cardiac gating and may, therefore, also be used for simultaneous evaluation of myocardial iron. The tissue signal intensities were measured from spin echo images and the myocardium muscle signal intensity ratio was determined. The SI ratio was converted to tissue iron concentration values based on a modified calibration curve from the liver model. The crucial steps of the method were optimized; i.e. recognition and selection of the myocardial slice for analysis and positioning of the regions of interest (ROIs) within the myocardium and the skeletal muscle. This made the myocardial MRI measurements sufficiently reproducible. We applied this method in 41 multiply transfused patients. Our data demonstrate significant positive linear relationships between different iron store parameters and the MRI-derived myocardial iron concentration, which was significantly related to the serum ferritin concentration (ρ = 0.62.P < 0.0001) and to the MRI-determined liver iron concentration (ρ = 0.36,P = 0.02). The myocardial MRI iron concentrations demonstrated also a significant positive correlation with the number of blood units given (ρ = 0.45,P = 0.005) and the aminotransferase serum concentration (ρ = 0.54,P = 0.0008). Our data represents indirect evidence for the ability of MRI techniques based on myocardium/muscle signal intensity ratio measurements to evaluate myocardial iron overload.     

MR imaging of degenerative disc disease in the lumbar spine with ultrashort TE pulse sequences

Objective The objective of this study was to assess the feasibility of using ultrashort TE (UTE) pulse sequences to image the lumbar spine.Materials Pulse sequences of TE=0.08 ms were used to image the lumbar spine in 5 normal subjects and 14 patients with degenerative disease. Contrast enhancement was administered in 11 cases.Results The sequences showed high signal in the anterior and posterior longitudinal ligaments, the cartilaginous end plate, the annulus fibrosus, the ligamentum flavum, interspinous ligaments and insertions of ligaments. Normal contrast enhancement was seen in these structures. Enhancement of hypertrophied ligaments and scar tissue was readily identified. Long T2 suppression techniques were useful in distinguishing enhancement of scar tissue from veins. Enhancement in discs was more obvious than with conventional sequences. In a case of thalassaemia bands of high signal were seen in the intervertebral discs parallel to the end plates.Conclusion The UTE sequences offer new options for visualizing discs, scar tissue, ligaments and other structures of the lumbar spine in health and disease.     

ECG-gated <Superscript>23</Superscript>Na-MRI of the human heart using a 3D-radial projection technique with ultra-short echo times

Pathological changes in tissue often manifest themselves in an altered sodium gradient between intra- and extracellular space due to a malfunctioning Na⁺–K⁺ pump, resulting in an increase in total sodium concentration in ischaemic regions. Therefore, ²³Na-MRI has the potential to non-invasively differentiate viable from non-viable tissue by detecting concentration changes of intra- and extracellular sodium. As the in vivo sodium signal shows a bi-exponential T₂ decay, with a short component of less than 1 ms, the accurate quantification of the total sodium content requires imaging techniques with ultra-short echo times (TE) below 0.5 ms. A 3D-radial projection technique has been developed which allows the acquisition of ECG-triggered sodium images of the human heart with a TE of 0.4 ms. With this pulse sequence ²³Na-MRI volunteer measurements of the head or the heart were performed in less than 18 min on a 1.5-T clinical scanner with an isotropic resolution of 10 mm³. The signal to noise ratio of the radial projection technique is twofold higher than that of a Cartesian gradient echo pulse sequence (TE = 3.2 ms). Radial ²³Na-MRI provides a tool for clinical studies, aiming at the differentiation of viable and non-viable tissue.     

Characterization of late radiation effects in the rat thoracolumbar spinal cord by MR imaging using USPIO

The aim of this study was to detect late radiation effects in the rat spinal cord using MR imaging with ultra-small particles of iron oxide (USPIO) contrast agent to better understand the development of late radiation damage with emphasis on the period preceding neurological signs. Additionally, the role of an inflammatory reaction was assessed by measuring macrophages that internalized USPIO. T₂-weighted spin echo MR measurements were performed at 7T in six rats before paresis was expected (130–150 days post-irradiation, early group), and in six paretic rats (150–190 days post-irradiation, late group). Measurements were performed before, directly after and, only in the early group, 40 h after USPIO administration and compared with histology. In the early group, MR images showed focal regions in grey matter (GM) and white matter (WM) with signal intensity reduction after USPIO injection. Larger lesions with contrast enhancement were located in and around edematous GM of three animals of the early group and five of the late group. Forty hours after injection, additional lesions in WM, GM and nerve roots appeared in animals with GM edema. In the late paretic group, MR imaging showed WM necrosis adjacent to areas with large contrast enhancement. In conclusion, detection of early focal lesions was improved by contrast administration. In the animals with extended radiation damage, large hypo-intense regions appeared due to USPIO, which might be attributed to blood spinal cord barrier breakdown, but the involvement of blood-derived iron-loaded macrophages could not be excluded.     

In vivo 13C chemical shift imaging of the human liver

Chemical shift imaging (CSI) was applied to measure natural abundance proton-decoupled¹³C-NMR spectra of the human liver. Large surface coils were designed for¹³C spectra acquisition (16-cm-diameter circular coil) as well as for proton imaging and decoupling (21×20-cm butterfly coil). Such sizes allowed deep observations of the abdomen. A space matrix of 8×4 voxels (4×8 cm each) was defined using 32 phase-encoding steps. Magnetic field gradients were adjusted on multicompartment phantoms to limit contamination between voxels. Spectral maps containing {¹H}-¹³C spectra of liver from healthy volunteers with an acceptable signal-to-noise ratio were recorded within 20 min. Liver spectra exhibited well-defined resonances corresponding to fatty acyl chains, carbonyl groups, and sugars. The (C-l)-glycogen resonance was also detected under such conditions. Such a technique would be of interest in the development of metabolic investigations on the human liverin vivo.     

装备自动定向系统中步进电动机的开发应用

在简要介绍一种基于步进电动机控制的自动化定向系统技术方案的基础上,着重分析了步进电动机高精度细分中的几个具体技术问题。