(31)P-MR Spectroscopy for the evaluation of energy metabolism in intact residual myocardium after acute myocardial infarction in humans

Objective experimental studies have demonstrated that acute myocardial infarction (MI) alters energy metabolism even in non-infarcted adjacent tissue. In patients with subacute MI, the influence of the regional ischemie insult on energy metabolism of intact septal myocardium was analyzed using³¹P-Magnetic resonance spectroscopy (MRS). Patients and Methods in eight patients with wall motion abnormalities in the anterior wall³¹P-spectra were obtained from non-infarcted adjacent scptal myocardium, as well as infarcted anterior myocardium (voxel size 25 ccm each) 29 ±8 days after MI using a 3D-CSI technique. Additionally, cardiac function was analyzed using breath-hold cine MRI. MR1 was repeated 6 months after revascularization to assess viability of infarcted segments. Eight age-matched healthy volunteers served as control group. Results according to follow-up MRI 4/8 patients showed regional wall motion recovery. Here, PCr/ATP-ratios were not significantly reduced in intact septal myocardium as well as infarcted anterior myocardium compared to healthy volunteers (1.28 ±0.10 and 1.14 ±0.09 vs. 1.45 ±0.29). No recovery of regional function was detected in 4/8 patients with —therefore—non-viable anterior myocardium. PCr/ATP-ratios were significantly reduced in intact and infarcted myocardium compared with healthy volunteers as well as to patients with wall motion recovery (0.77 ±0.17 and 0.49 ±0.23;P < 0.05). Discussion these preliminary results indicate that energy metabolism is reduced in patients with persisting wall motion abnormalities after myocardial infarction and revascularization in ischemically injured as well as in adjacent non-injured myocardium.     

Clinical assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA

This study assessed the accuracy and feasibility of magnetic resonance imaging (MRI) during a constant infusion of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) for the determination of myocardial viability in patients with recent acute myocardial infarction (AMI). Nine patients were studied within 10 days of AMI. Rest-redistribution 201Thallium (201Tl) single photon emission computed tomography (SPECT) was used as a gold standard for viability. Using MRI, regional perfusion was assessed using dynamic imaging during a bolus injection of Gd-DTPA and viability was assessed during a continuous infusion. Finally, cine MR images were acquired at baseline, during low-dose dobutamine infusion and after recovery. To assess viability, the left ventricle was divided into 16 segments and signal intensity in corresponding MRI and redistribution SPECT segments were compared. Wall thickening index (WTI) was determined at each step during the dobutamine study. The results revealed that in five patients, reduced perfusion in infarcted regions was observed qualitatively during dynamic first pass imaging. There was a significant inverse correlation between 201Tl uptake and MRI signal intensity, i.e. infarcted tissue (low 201Tl uptake) had increased MR signal intensity. Segments were separated into normal (201Tl uptake > 90%) and infarcted (< 601%). lnfarcted MRI segments had greater signal intensity than normal segments (179 +/- 50 vs. 102 +/- 14%; P < 0.0001). WTI in normal segments increased by 18 +/- 8.5% (P < 0.0001) from baseline to 10 microg/kg per min of dobutamine while infarcted tissue WTI decreased 2.8 +/- 7.2% (P = 0.17). Thus regions of myocardium that were infarcted as defined by reduced 201Tl uptake and absent contractile reserve showed greatly increased MRI signal intensity during a constant infusion of Gd-DTPA. The use of MRI during a constant infusion of Gd-DTPA is accurate and feasible for the determination of myocardial necrosis in a clinical setting.     

Clinical assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA

This study assessed the accuracy and feasibility of magnetic resonance imaging (MRI) during a constant infusion of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) for the determination of myocardial viability in patients with recent acute myocardial infarction (AMI). Nine patients were studied within 10 days of AMI. Rest-redistribution²⁰¹Thallium (²⁰¹Tl) single photon emission computed tomography (SPECT) was used as a gold standard for viability. Using MRI, regional perfusion was assessed using dynamic imaging during a bolus injection of Gd-DTPA and viability was assessed during a continuous infusion. Finally, cine MR images were acquired at baseline, during low-dose dobutamine infusion and after recovery. To assess viability, the left ventricle was divided into 16 segments and signal intensity in corresponding MRI and redistribution SPECT segments were compared. Wall thickening index (WTI) was determined at each step during the dobutamine study. The results revealed that in five patients, reduced perfusion in infarcted regions was observed qualitatively during dynamic first pass imaging. There was a significant inverse correlation between²⁰¹Tl uptake and MRI signal intensity, i.e. infarcted tissue (low²⁰¹Tl uptake) had increased MR signal intensity. Segments were separated into normal (²⁰¹Tl uptake >90%) and infarcted (<60%). Infarcted MRI segments had greater signal intensity than normal segments (179±50 vs. 102±14%;P<0.0001). WTI in normal segments increased by 18±8.5% (P<0.0001) from baseline to 10 μg/kg per min of dobutamine while infarcted tissue WTI decreased 2.8±7.2% (P=0.17). Thus regions of myocardium that were infarcted as defined by reduced²⁰¹Tl uptake and absent contractile reserve showed greatly increased MRI signal intensity during a constant infusion of Gd-DTPA. The use of MRI during a constant infusion of Gd-DTPA is accurate and feasible for the determination of myocardial necrosis in a clinical setting.     

Long-term follow-up of patients with acute myocarditis by magnetic resonance imaging

Magnetic resonance imaging (MRI) reveals cardiac signal intensity changes in patients with acute myocarditis; however, the natural history of these changes and their relationship to individual outcomes are unknown. The relationship of MRI findings to long-term outcome was studied by serial MRI studies in 16 patients with acute myocarditis who were followed for 30±4 (SE) months. Myocardial contrast enhancement was monitored using contrast-enhanced T1-weighted fast spin-echo images. Left ventricular ejection fraction was measured with gradient-echo sequences. Clinical symptoms were scored. The results were compared to a control group of 26 age-matched, healthy volunteers. Myocardial contrast enhancement, which was markedly increased in the early course of the disease, decreased at 4 weeks and remained within the normal range in most patients after 30 months. Contrast enhancement 4 weeks after onset of symptoms was predictive for the functional and clinical long-term outcome. Contrast-enhanced MRI may be a useful, noninvasive tool for long-term follow-up of patients with acute myocarditis. Furthermore, relatively early MRI findings may predict longer-term outcomes. Electronic Publication     

Quantitative assessment of regional myocardial function in a rat model of myocardial infarction using tagged MRI

We characterized global and regional left ventricular (LV) function during post myocardium infarction (MI) remodeling in rats, which has been incompletely described by previous MRI studies. To assess regional wall motion, four groups of infarcted animals corresponding to 1–2, 3–4, 6–8 and 9–12 weeks post-MI respectively were imaged using a fast gradient echo sequence with a 2D spatial modulation of magnetization (SPAMM) tagging preparation. An additional group was serially imaged (1–2 and 6–7 weeks post-MI) to assess the global function. Regional and global functional parameters of infarcted rats were compared to non-infarcted normal rats. Compared to normal rats, a decrease in ejection fraction (70 ±7 vs. 40 ± 8%, p<0.05) was observed in rats with MI. Maximal and minimal principal stretches (₁, ₂) and strains (E₁, E₂), principal angle () and displacement varied regionally in normal rats but deviated significantly from the normal values in rats with MI particularly in the infarcted and adjacent zones. Not only was strain magnitude reduced segmentally post-MI, but strain direction became more circumferentially oriented, particularly in rats with larger infarctions. We report the first regional myocardial strain values in normal and infarcted rats. These results parallel findings in humans, and provide a unique tool to examine regional mechanical influences on the remodeling process.     

Signal enhancement through heteronuclear polarisation transfer in in-vivo <Superscript>31</Superscript>P MR spectroscopy of the human brain

Significant ³¹P NMR signal enhancement through heteronuclear polarisation transfer was obtained in model solutions and in vivo on a 1.5-T whole-body MR scanner equipped with two RF channels. The much higher population differences involved in proton Zeeman energy levels can be transferred to the ³¹P levels with the refocused INEPT (insensitive nucleus enhancement by polarisation transfer) double-resonance experiment by means of a series of simultaneously applied broadband RF pulses. INEPT achieves a polarisation transfer from ¹H to ³¹P spin states by directly reordering the populations in spin systems with heteronuclear scalar coupling. Thus, only the ³¹P NMR signal of metabolites with scalar ¹H–³¹P coupling is amplified, while the other metabolite signals in the spectra are suppressed. Compared to Ernst-angle excitation, a repetition-time-dependent signal enhancement of η=(29±3)% for methylene diphosphonic acid (MDPA) and η=(56±1)% for phosphorylethanolamine (PE) was obtained on model solutions through optimisation of the temporal parameters of the pulse experiment. The results are in good agreement with numerical calculations of the theoretical model for the studied spin systems. With optimised echo times, in-vivo ³¹P signal enhancement of the same order was obtained in studies of the human brain.     

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.     

Subacute myocardial infarction: assessment by STIR T2-weighted MR imaging in comparison to regional function

Purpose Increased T2 signal intensity (SI) can be regularly observed in myocardial infarction. However, there are controversial reports about the relationship of elevated T2 SI to myocardial viability and some authors propose that high T2 SI serves as a sign of irreversible myocardial injury. This study investigates increased T2 SI compared to myocardial function in patients with reperfused subacute myocardial infarction. Preserved function was used as criterion for viability. Methods Ten healthy volunteers and 17 patients with myocardial infarction and patent inlarct related coronary artery were examined on a 1.5 T Magnetom Vision system (Siemens). For T2-weighted MR imaging a breath-hold STIR sequence with dark-blood preparation was used. Cine FLASH 2D imaging was applied to assess myocardial function. Signal-to-noise (S/N) in STIR T2 images was measured in normal and infarcted regions and subsequently identified by two independent observers. Based on a 20 segment model of the left ventricle findings were compared to regional myocardial function. Results Elevated STIR T2 SI was found in all 17 patients and observed in 27% (204/754) of segments. S/N of normal myocardium was 5.1 ±0.7 in volunteers and 4.9 ± 0.8 in patients(P=NS). Infarcted myocardium presented with significantly-increased S/N 12.8 ± 1.9 (P < 0.0001). Significant transmural elevation of T2 SI was noted in 32% of segments with preserved systolic function. Conclusion Increased STIR T2 SI can be observed transmurally in post-ischemic myocardial regions with preserved function. It therefore cannot be used as an exclusive marker for the non-viable region.     

In vivo quantification of response to treatment in patients with multiple myeloma by <Superscript>1</Superscript>H magnetic resonance spectroscopy of bone marrow

Object Magnetic resonance imaging (MRI) is the gold standard non-invasive technique to detect malignant disease in the bone marrow. Proton magnetic resonance spectroscopy (MRS) can be performed as a quick adjunct to routine spinal MRI. We performed proton MRS to patients with multiple myeloma (MM) at diagnosis and after treatment to investigate the possible correlation of MRS data with response to therapy. Patients and methods Twenty-one patients with newly diagnosed MM underwent combined MRI/MRS explorations of a transverse center section in the fifth lumbar vertebral body. MRS was acquired with STEAM and 40 ms TE. Areas of unsuppressed water and lipid resonances were used to calculate the lipid-to-water ratio (LWR). Results No association was detected between initial LWRs and the clinical characteristics of patients. Post treatment MRS was available in 16 patients of whom 11 (69%) presented an LWR increase, this included all complete responders (8/8, 100%, P = 0.012). A post-treatment LWR value equal to or larger than one is proposed as a non-invasive marker of complete response to treatment. Conclusion Only patients responding to treatment presented a significant increase in bone marrow LWR after therapy. MRS may provide an adequate quantification of response to chemotherapy in patients with MM.     

Assessment of myocardial perfusion using contrast-enhanced MR imaging: Current status and future developments

Excellent inherent tissue contrast is one of the great promises of clinical magnetic resonance (MR) imaging, but functional information is relatively limited. However, MR imaging complemented by the administration of contrast agents can provide such functional assessment. The perfusion status of the myocardium is one of the most important functional information in cardiovascular imaging. Because the clinical acceptance of a contrast agent is measured by its ability to improve patient outcome and to guide therapy, it is unlikely that detection of myocardial infarction, the final stage of ischemic heart disease, should be the target for contrast media development. It would obviously be better if occult regional myocardial perfusion deficits could be reliably detected. The current article was prepared to help the clinical radiologist to keep pace with new strategies for myocardial enhancement and their potential clinical applicability for detection of early perfusion deficits. Several techniques for noninvasive measurement of myocardial perfusion are currently evolving which have the potential to be introduced into routine MR imaging. Most investigators favor a first-pass analysis of the contrast agent bolus through the myocardium using ultrafast sequences. However, such a technique may require clinical introduction of a blood pool agent. There are good resons to favorT ₁-weighted sequences over susceptibility imaging in such first-pass studies. In the future, assessment of myocardial perfusion status using contrast-enhanced MR imaging may be done producing perfusion maps with high spatial resolution (e.g., 256×128), with sequences available on most scanners without special hardware requirements (e.g., IR-Turboflash, keyhole imaging), and requiring only a short period of time for examination (≈3 min).     

MRI of the lung using hyperpolarized <Superscript>3</Superscript>He at very low magnetic field (3 mT)

Optical pumping of ³He produces large (hyper) nuclear-spin polarizations independent of the magnetic resonance imaging (MRI) field strength. This allows lung MRI to be performed at reduced fields with many associated benefits, such as lower tissue susceptibility gradients and decreased power absorption rates. Here we present results of 2D imaging as well as accurate 1D gas diffusion mapping of the human lung using ³He at very low field (3 mT). Furthermore, measurements of transverse relaxation in zero applied gradient are shown to accurately track pulmonary O₂ partial pressure, opening the way for novel imaging sequences.     

In situ and minimally invasive breast cancer: morphologic and kinetic features on contrast-enhanced MR imaging

Purpose: This retrospective study was undertaken to investigate the morphologic and dynamic features of in situ and minimally invasive breast cancer on contrast-enhanced (c.-e.) MR imaging and to examine possible associations to pathology features. Material and methods: A total of 71 patients underwent MR imaging. T1-weighted FLASH-3D images were obtained before and after intravenous administration of Gd-DTPA. Histopathologic analysis of 78 lesions revealed ductal carcinoma in situ (DCIS)n=50 and DCIS with microinvasionn=28. MR features were correlated with histopathologic findings. Results: Enhancement in DCIS was focal (73%), diffuse (10%) or ductal (17%). No enhancement occurred in two cases (4%). In 65% enhancement speed was classified as delayed. There was a tendency toward a more ill-defined (83 vs. 43%) enhancement pattern in high grade DCIS and a more ductal (29 vs. 12%) and faster (50 vs. 29%) enhancement in comedo type DCIS. However, significant differences in the enhancement behaviour could neither be demonstrated between high grade and non high grade DCIS nor between comedo and non comedo type DCIS. No significant differences were noted between pure and microinvasive DCIS. Conclusion: In this retrospective analysis the majority (96%) of DCIS lesions show contrast enhancement. However, in only about 50% of DCIS the criteria of a so-called ‘typical’ enhancement behaviour was fulfilled, that means strong, early, focal ill-circumscribed or ductal. Enhancement that follows a duct is often associated with malignancy, however this feature was only present in 17% of the cases. c.-e. MR imaging allowed the detection of 25 additional foci of DCIS. Therefore malignant in situ lesions can be present with atypical enhancement, and should be taken into consideration in high-risk patients in particular.     

Fatty metaplasia quantification and impact on regional myocardial function as assessed by advanced cardiac MR imaging

Objective

This study aimed to investigate the advantages of recently developed cardiac imaging techniques of fat–water separation and feature tracking to characterize better individuals with chronic myocardial infarction (MI).

Materials and methods

Twenty patients who had a previous MI underwent CMR imaging. The study protocol included routine cine and late gadolinium enhancement (LGE) technique. In addition, mDixon LGE imaging was performed in every patient. Left ventricular (LV) circumferential (Ecc_LV) and radial (Err_LV) strain were calculated using dedicated software (CMR⁴², Circle, Calgary, Canada). The extent of global scar was measured in LGE and fat–water separated images to compare conventional and recent CMR imaging techniques.

Results

The infarct size derived from conventional LGE and fat–water separated images was similar. However, detection of lipomatous metaplasia was only possible with mDixon imaging. Subjects with fat deposition demonstrated a significantly smaller percentage of fibrosis than those without fat (10.68 ± 5.07% vs. 13.83 ± 6.30%; p = 0.005). There was no significant difference in Ecc_LV or Err_LV between myocardial segments containing fibrosis only and fibrosis with fat. However, Ecc_LV and Err_LV values were significantly higher in myocardial segments adjacent to fibrosis with fat deposition than in those adjacent to LGE only.

Conclusions

Advanced CMR imaging ensures more detailed tissue characterization in patients with chronic MI without a relevant increase in imaging and post-processing time. Fatty metaplasia may influence regional myocardial deformation especially in the myocardial segments adjacent to scar tissue. A simplified and shortened myocardial viability CMR protocol might be useful to better characterize and stratify patients with chronic MI.

     

Effects of Al<Superscript>3+</Superscript> substitution on the luminescence properties of LuNbO<Subscript>4</Subscript> doped with Eu<Superscript>3+</Superscript> and Tb<Superscript>3+</Superscript> ions

The effect of Al³⁺ substitution on the enhancement of the luminescence of Lu_1–xAl_xNbO₄:Eu³⁺ and Lu_1–xAl_xNbO₄:Tb³⁺ was investigated. X-ray diffraction patterns confirmed that the Eu³⁺, Tb³⁺, and Al³⁺ ions were fully incorporated into the Lu³⁺ sites. In the case of Lu_1–xAl_xNbO₄:Eu³⁺, the predominant red emission (614 nm) was assigned to the ⁵D₀?→?⁷F₂ transition of Eu³⁺ and for x?=?0–0.05, its intensity increased up to ~125 and 108% under 395 nm (⁷F₀ → ⁵L₆) and a charge transfer band excitation, respectively. For Lu_1–xAl_xNbO₄:Tb³⁺, the strongest emission band peaking at 551 nm was attained in the green region among multiple emission bands corresponding to the ⁵D₄?→?⁷F_J transitions of Tb³⁺. Increasing the x values from 0 to 0.05 increased the green emission significantly by ~137%. These phenomena were explained by the local structural distortions and crystal field asymmetry surrounding Eu³⁺ and Tb³⁺, which were attributed to a large difference in the ionic radii of Al³⁺ and Lu³⁺.     

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.     

In situ and minimally invasive breast cancer: morphologic and kinetic features on contrast-enhanced MR imaging

PURPOSE: This retrospective study was undertaken to investigate the morphologic and dynamic features of in situ and minimally invasive breast cancer on contrast-enhanced (c.-e.) MR imaging and to examine possible associations to pathology features. MATERIAL AND METHODS: A total of 71 patients underwent MR imaging. T1-weighted FLASH-3D images were obtained before and after intravenous administration of Gd-DTPA. Histopathologic analysis of 78 lesions revealed ductal carcinoma in situ (DCIS) n = 50 and DCIS with microinvasion n = 28. MR features were correlated with histopathologic findings. RESULTS: Enhancement in DCIS was focal (73%), diffuse (10%) or ductal (17%). No enhancement occurred in two cases (4%). In 65% enhancement speed was classified as delayed. There was a tendency toward a more ill-defined (83 vs. 43%) enhancement pattern in high grade DCIS and a more ductal (29 vs. 12%) and faster (50 vs. 29%) enhancement in comedo type DCIS. However, significant differences in the enhancement behaviour could neither be demonstrated between high grade and non high grade DCIS nor between comedo and non comedo type DCIS. No significant differences were noted between pure and microinvasive DCIS. CONCLUSION: In this retrospective analysis the majority (96%) of DCIS lesions show contrast enhancement. However, in only about 50% of DCIS the criteria of a so-called 'typical' enhancement behaviour was fulfilled, that means strong, early, focal ill-circumscribed or ductal. Enhancement that follows a duct is often associated with malignancy, however this feature was only present in 17% of the cases. c.-e. MR imaging allowed the detection of 25 additional foci of DCIS. Therefore malignant in situ lesions can be present with atypical enhancement, and should be taken into consideration in high-risk patients in particular.     

Contrast enhancement in atherosclerosis development in a mouse model: in vivo results at 2 Tesla

To develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE^–/– mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T1 spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 m spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice.     

An oxygen-consuming phantom simulating perfused tissue to explore oxygen dynamics and <Superscript>19</Superscript>F MRI oximetry

Objective  

This study presents a reproducible phantom which mimics oxygen-consuming tissue and can be used for the validation of ¹⁹F MRI oximetry.     

Assignment of the 2.03 ppm resonance in in vivo <Superscript>1</Superscript>H MRS of human brain tumour cystic fluid: contribution of macromolecules

MRI and MRS are established techniques for the evaluation of intracranial mass lesions and cysts. The 2.03 ppm signal recorded in their ¹H-MRS spectra is often assigned to NAA from outer volume contamination, although it has also been detected in non-infiltrating tumours and large cysts. We have investigated the molecular origin of this resonance in ten samples of cystic fluids from human brain tumours. The NMR detected content of the 2.03 ppm resonance in 136 ms echo time spectra, assuming an N- CH₃ origin, was 3.19 ± 1.01 mM. Only one third (34 ± 12%) of the N-acetyl containing compound (NAC) signal could be extracted by perchloric acid (PCA) indicating that most of it originated in a macromolecular PCA-insoluble component. Chemical analysis of the cyst fluids showed that sialic acid bound to macromolecules would account for 64.3% and hexuronic containing compounds for 29.2% of the NMR-detectable ex vivo signal, 93.4% of the signal at TE 136 ms. Lactate content measured by NMR (6.4 ± 4.4 mM) and the predominance of NAC originating in sialic acid point to a major origin from tumour rather than from plasma for this 2.03 ppm resonance.     

<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.