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.     

(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.     

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.     

Determination of in vivo rat muscle Gd-DTPA relaxivity at 6.3 T

For the in vivo relaxivity of Gd-DTPA at 6.3 T in rat muscle a value of 2.7±0.5 (mM s)⁻¹ was found, and for the in vitro value in water 3.00±0.56 (mM s)⁻¹ at 37°C. The temperature dependence of the in vitro relaxivity was −0.087 (mM s °C)⁻¹. The relation between1/T ₁ and the tissue Gd-DTPA concentration is linear for the normally used in vivo Gd-DTPA concentration range     

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.     

Detection of myocardial viability in acute infarction using contrast-enhanced <Superscript>1</Superscript>H magnetic resonance imaging

Background Reperfusion strategies salvage myocardium at risk in acute myocardial infarction (MI). This clinical study was performed to determine whether areas without evidence of delayed MRI contrast enhancement in MI correspond to viability by means of percent systolic wall thickening (%SWT) and enddiastolic wall thickness (EDWT) in chronic infarction. Methods Twenty MRI studies were performed in ten patients within 6 days of MI and 3 months post-MI. On a segmental basis the percentage of viable myocardium as defined by contrast-enhanced MRI (no delayed MRI contrast enhancement) in acute MI was measured and was compared with %SWT and EDWT in chronic MI. Results Of the 1718 segments in acute infarction in which the percentage of viable myocardium was measured 1333 were found to be completely viable by means of contrast-enhanced MRI (no delayed MRI contrast enhancement). All of these segments revealed %SWT on day 90 post-MI, and 97% of segments were viable by means of an EDWT of more than 5.5 mm. In 85 segments the proportion of viable myocardium was 50–99% (mean 56±8%), with 92% segments found to be viable by means of %SWT and 92% by EDWT, and of 156 segments with viable myocardium between 1–49% (36±8%) 79% were found to be viable by means of %SWT and 82% by EDWT. Corresponding proportions of 144 segments with transmural delayed MRI contrast enhancement in acute MI were 45% and 17%. Conclusions In acute reperfused MI viable myocardium as delineated by contrast-enhanced MRI is correlated with clinical parameters of viability. Delayed MRI contrast enhancement resolves nontransmural MI and may become a valuable clinical tool when planning revascularization procedures.     

Magnetic resonance imaging differentiation of adrenal masses at 1.5 t: t2-weighted images,chemical shift imaging,and gd-dtpa dynamic studies

The purpose of our study was to assess the potential role of spin-echo (SE), chemical shift, and gadolinium-enhanced magnetic resonance imaging (MRI) in the differentiation of adrenal masses.Seventy-two adrenal masses (26 nonhyperfunctioning adenomas, 16 aldosterone-secreting adenomas and 6 other different benign cortical masses, 18 pheochromocytomas, and 6 malignant masses) in 63 patients were evaluated with spin-echo sequences, chemical shift imaging (CSI) and gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) dynamic studies. Ratios and indices of signal intensity for all examined MRI methods were calculated and examined for significance of difference between different types of adrenal masses.Quantitative magnetic resonance evaluation of adrenal masses showed significant differences (at least<0.01) between nonhyperfunctioning adenomasvs. pheochromocytomas orvs. malignant lesions orvs. aldosterone-secreting adenomas and between pheochromocytomasvs. malignant lesions. The most specific indicators of adrenal mass character proved to be the CSI ratio based on opposed-phase and in-phase two-dimensional fast low-angle shot (FLASH) images, reflecting lipid content in the lesion, and Gd-DTPA dynamic studies ratios reflecting contrast agent inflow and washout in the lesion: Wo_max/last and Dyn_1.2–3.2. There was no overlap of CSI ratio between adenomas and pheochromocytomas. The overlap of ranges of CSI ratio between nonhyperfunctioning adenomas and aldosterone-secreting adenomas was only 18.5%. There was no overlap of Wo_max/last ratio between adenomas and pheochromocytomas, or adenomas and malignant lesions. The overlap of ranges of Dyn_{1.2– 3.2} ratio between pheochromocytomas and malignant lesions was only 17.6%.MRI enables good visualization and specific characterization of adrenal masses. The optimal MRI protocol for the adrenal region is presented.Address for correspondence: Imaging Department, Warsatv Province Hospital, ul. Kondratowicza 8, 03-285 Warsaw, Poland.     

Distribution of gadomelitol in a human breast tumor model in mice

The study evaluates the tumor distribution of the rapid clearance blood pool agent (RCBPA) gadomelitol, in a breast tumor model. Different techniques were used : (1) tissue gadolinium concentrations measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES), (2) whole body quantitative autoradiography using radiolabeled [¹⁵³Gd] gadomelitol and (3) dynamic contrast-enhanced MRI with compartmental analysis. An accumulation of gadomelitol in tumors compared to muscle was observed 30 min and 3 h post injection (p.i.). Thirty minutes p.i., the gadomelitol tumor distribution evaluated by autoradiography showed a marked difference between the rim and the center, whereas both areas showed comparable concentrations after 3 h. Using dynamic contrast-enhanced MRI, three phases could be observed during the 1 hour observation period: (1) rapid tumor uptake within the first few minutes post-injection (2) a progressive increase in tumor signal enhancement over 10 min and (3) a steady-state phase. Average +/− SD (n=5) transendothelial permeability K^PS and the fractional blood volume fBV were 12.2±1.6 μl/min⁻¹/g and 5.4±0.2% respectively. Due to its slow extravasation and high tumor residence time, gadomelitol may potentially be useful to improve characterization between benign versus malignant tumors using dynamic MRI.     

High-resolution magnetic resonance imaging of iron-labeled myoblasts using a standard 1.5-T clinical scanner

Myoblast transplantation is a promising means of restoring cardiac function in infarcted areas. For optimization of transplant protocols, tracking the location and fate of the injected cells is necessary. An attractive imaging modality for this is magnetic resonance imaging (MRI) as it is noninvasive and as iron-labeled myoblasts provide a signal attenuation in T2*-weighted protocols. The aim of this study was to develop an efficient iron-labeling protocol for myoblasts and to visualize single-labeled cells using a clinical 1.5-T scanner. Pig myoblasts were labeled with a superparamagnetic iron oxide (SPIO) agent using a liposome transfection agent. Labeling efficiency, toxicity, cell viability, and proliferative capacity were measured for 10 days. Magnetic resonance (MR) of myoblast cultures used a T2*-weighted three-dimensional protocol with a maximum in-plane resolution of 19.5 × 26.0 m² and 50 m slices. Use of liposomes improved SPIO labeling efficiency. Labeling did not induce toxicity or affect cell viability or proliferation. The cell distribution as observed with light and fluorescence microscopy matched the signal voids observed in the MRI datasets. Liposomes promote fast, nontoxic and efficient SPIO labeling of myoblasts that can be tracked by MRI microscopy in clinical scanners using susceptibility-weighted protocols.     

Gadolinium-containing copolymeric chelates—a new potential MR contrast agent

Rationale and objectives: To develop and partially characterize a new class of potential blood pool magnetic resonance (MR) contrast agents.Methods: Various copolymeric chelates of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) were prepared with differing molecular weights of polyethylene glycol (PEG) or polypropylene glycol (PPG) as linkers between the monomeric chelate units. Gadolinium content of the polymeric chelates was determined by atomic absorption spectra. Relaxivity of the polymeric chelates was measured at 1.5 Tesla and compared with Gadolinium-DTPA. MR angiography (MRA) was performed in rabbits comparing Gd-DTPA with Gd-copolymers.Results: The gadolinium content of the copolymeric chelates ranged from 2.95 to 22.2% on weight basis. The molecular weight of the PEG linkers in the copolymers ranged from about 150 to about 3400. Ther ₁ (1/T1, mM⁻¹ s⁻¹) for Gd-DTPA=4.1. Ther ₁ values for the different Gd-containing polymers ranged from 3.8 to 5.8, with the lowestr ₁ for the polymer prepared with the lowest-molecular-weight complex. The higher-molecular-weight complexes resulted in moderately higher relaxivity. MRA with Gd-copolymers, in rabbits, showed markedly greater vascular enhancement relative to an equivalent dose of Gd-DTPA. Vascular enhancement was much more sustained with the copolymeric agent and confined to vascular space; i.e. no appreciable background tissue enhancement—a reflection of distribution into extravascular fluid space—was observed.Conclusions: Relative to Gd-DTPA monomers, PEG-containing Gd-DTPA polymeric complexes provided moderate increases in relaxivity but markedly greater efficacy during in vivo MRA. In vitro relaxivity studies of Gd-copolymers showed only an approximately 50% increase inr ₁ relaxivity compared with Gd-DTPA. The PEG-containing complex's lack of rigidity may have diminished the effect of spin diffusion on relaxation, thereby accounting for this modest increase. The greater efficacy of Gd-copolymers during in vivo MRA may reflect compartmentalization within the vascular space and possibly enhanced relaxation of the macromolecular copolymers in the blood. Gd-copolymers are promising agents that merit additional study.     

23Na chemical shift imaging in the living rat brain using a chemical shift agent,Tm[DOTP]5–

Objective

It is well known that the use of shift reagents (SRs) in nuclear magnetic resonance (NMR) studies is substantially limited by an intact blood–brain barrier (BBB). The current study aims to develop a method enabling chemical shift imaging in the living rat brain under physiological conditions using an SR, Tm[DOTP]⁵⁻.

Materials and methods

Hyperosmotic mannitol bolus injection followed by 60 min infusion of a Tm[DOTP]⁵⁻ containing solution was administered via a catheter inserted into an internal carotid artery. We monitored the homeostasis of physiological parameters, and we measured the thulium content in brain tissue post mortem using total reflection fluorescence spectroscopy (T-XRF). The alterations of the ²³Na resonance spectrum were followed in a 9.4T small animal scanner.

Results

Based on the T-XRF measurements, the thulium concentration was estimated at 2.3 ± 1.8 mM in the brain interstitial space. Spectroscopic imaging showed a split of the ²³Na resonance peak which became visible 20 min after starting the infusion. Chemical shift imaging revealed a significant decrease of the initial intensity level to 0.915 ± 0.058 at the end of infusion.

Conclusion

Our novel protocol showed bulk accumulation of Tm[DOTP]⁵⁻ thus enabling separation of the extra-/intracellular ²³Na signal components in the living rat brain while maintaining physiological homeostasis.

     

Quantitative T 2 * assessment of acute and chronic myocardial ischemia/reperfusion injury in mice

Object

Imaging of myocardial infarct composition is essential to assess efficacy of emerging therapeutics. T ₂ ^* mapping has the potential to image myocardial hemorrhage and fibrosis by virtue of its short T ₂ ^* . We aimed to quantify T ₂ ^* in acute and chronic myocardial ischemia/reperfusion (I/R) injury in mice.

Materials and methods

I/R-injury was induced in C57BL/6 mice (n?=?9). Sham-operated mice (n?=?8) served as controls. MRI was performed at baseline, and 1, 7 and 28?days after surgery. MRI at 9.4?T consisted of Cine, T ₂ ^* mapping and late-gadolinium-enhancement (LGE). Mice (n?=?6) were histologically assessed for hemorrhage and collagen in the fibrotic scar.

Results

Baseline T ₂ ^* values were 17.1?±?2.0?ms. At day 1, LGE displayed a homogeneous infarct enhancement. T ₂ ^* in infarct (12.0?±?1.1?ms) and remote myocardium (13.9?±?0.8?ms) was lower than at baseline. On days 7 and 28, LGE was heterogeneous. T ₂ ^* in the infarct decreased to 7.9?±?0.7 and 6.4?±?0.7?ms, whereas T ₂ ^* values in the remote myocardium were 14.2?±?1.1 and 15.6?±?1.0?ms. Histology revealed deposition of iron and collagen in parallel with decreased T ₂ ^* .

Conclusion

T ₂ ^* values are dynamic during infarct development and decrease significantly during scar maturation. In the acute phase, T ₂ ^* values in infarcted myocardium differ significantly from those in the chronic phase. T ₂ ^* mapping was able to confirm the presence of a chronic infarction in cases where LGE was inconclusive. Hence, T ₂ ^* may be used to discriminate between acute and chronic infarctions.     

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.     

1H NMR-based metabolomic identification of at-risk areas after myocardial infarction in swine

Object ¹H NMR-based metabolic profiling has been used to investigate areas of the heart after an acute myocardial infarction. Methods Tissue was obtained from control, at-risk (areas that survive within the infarct zone) and necrotic myocardium after 48 min of left anterior descending coronary artery occlusion and 2 h of reperfusion in a swine model. HR-MAS (high resolution magic angle spectroscopy) spectra from intact tissue and tissue extract spectra were obtained for each region and statistical models were built for each type of spectra allowing differentiation between control, at-risk and necrotic heart. Results At-risk and, especially, necrotic areas have a reduced concentration of NMR visible metabolites as compared to control tissue, total creatine (phosphorilated and unphosphorilated) being the single most important metabolite in the different discriminant models. Creatine concentration decreased from 18.28 ± 0.84 μmols/g fresh weight in controls to 12.58 ± 2.89 (P < 0.05) and 9.96 ± 2.21 (P < 0.01) in at-risk and necrotic areas, respectively. Taurine and myo-inositol were also involved in the discriminant models. HR-MAS spectra also showed an increase in lipid signals at 0.9 and 1.28 ppm as markers of necrotic tissue. These results support the view that the analysis of in vivo ¹H MRS may have value in differentiating normal, at-risk and infarcted myocardium. This work was supported by Red de Enfermedades Cardiovasculares (RECAVA) CICYT SAF2005-01758 and EU Grant FP6-513595.     

In vitro imaging of single living human umbilical vein endothelial cells with a clinical 3.0-T MRI scanner

Iron oxide-labelled, single, living human umbilical vein endothelial cells (HUVECs) were imaged over time in vitro using a clinical 3.0-T magnetic resonance (MR) microscopy system. Labelling efficiency, toxicity, cell viability, proliferation and differentiation were assessed using flow cytometry, magnetic cell sorting and a phenanthroline assay. MR images were compared with normal light and fluorescence microscopy. Efficient uptake of iron oxide into HUVECs was shown, although with higher label uptake dose-dependent cytotoxic effects were observed, affecting cell viability. For MR imaging, a T2* weighted three-dimensional protocol was used with in-plane resolution of 39×48μm² and 100-μm slices with a scan time of 13 min. MRI could detect living cells in standard culture dishes at single-cell resolution, although label loss was observed that corresponded with the intracellular iron measurements. MR microscopy using iron oxide labels is a promising tool for studying HUVEC migration and cell biology in vitro and in vivo, but possible toxic effects of label uptake and loss of label over time should be taken into account.     

Application of two-dimensional CSI for absolute quantification of phosphorus metabolites in the human liver

There have recently been a number of studies dealing with the absolute quantification of concentrations of MR-visible phosphorus compounds in different tissues. The use of absolute values rather than intensity ratios may furnish additional information about metabolic changes associated with different diseases. The purpose of this study was to develop a general procedure for measuring molar metabolite concentrations and to apply it with respect to the evaluation of human liver 31P-MRS data measured using a standard slice-selective two-dimensional CSI sequence and commercial¹H/³¹P surface coil. The experimental determination of all surface coil-related factors influencing signal intensity was undertaken using a gradient echo imaging technique that can be adapted to commercial systems. The resulting values for healthy volunteers (N = 9) showed concentrations of PME = 2.8 ± 1.3 mM, PDE = 9.9 ± 2.7 mM,P _i = 1.7 ± 0.7 mM, and ATP = 3.6 + 0.9 mM in the human liver. The data are quite consistent with published findings.     

Effects of partial volume and phase shift between fat and water in gradient-echo magnetic resonance-mammography

The signal modulations caused by partial volume effect and phase shift between fat and water signal in gradient-echo magnetic resonance mammography (GRE MR-mammography) have been calculated. Based on this, the theoretical sensitivity and specificity of GRE MR-mammography has been investigated considering different evaluation methods for the gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA)-based signal enhancement. The results show that both in- and out-of-phase sequences suffer from partial volume effects in voxels that contain both fat and water. This can decrease sensitivity to Gd-DTPA uptake in small, fat-embedded lesions or in pathology that contains fat interspersed histologically. Additionally, out-of-phase sequences can suffer from phase cancellation effects that can further decrease their sensitivity to Gd-DTPA uptake. In the worst case signal can actually decrease during Gd-DTPA influx. Determination of enhancement relative to the baseline value can decrease the specificity of GRE MR-mammography in the out-of-phase condition and decrease the sensitivity in the in-phase condition. These effects are less pronounced when enhancement is calculated relative to fat. These effects need to be understood since Gd-DTPA uptake is the prime indicator of malignancy in MR-mammography.     

T2 relaxation time study of iron overload in b-thalassemia

Myocardial iron deposition occurs as a result of blood transfusion therapy in b-thalassemia major patients. Since this deposition causes various cardiac complications, it is of interest to assess the iron content of the myocardium in relation to the clinical picture of the patients. Two different MRI indices were used to achieve this purpose: the T2 relaxation time and the heart/skeletal muscle signal intensity ratio. ECG gated spin echo images were obtained from 54 adult thalassemic patients, with a mean age of 26 (18–44) years, at TE = 22 ms and 60 ms, using a 1.5 T system. Patients were divided into 2 groups (A and B), according to their serum ferritin levels (> or < 2000 ng ml^-1). Results were compared with nine controls, with a mean age of 25 (18–43) years. Heart T2 relaxation time in controls (44.3 ± 3.5 ms) was higher than in group A (29.9 ± 5.7 ms,P< 0.001) and group B (33.4 ± 6.8 ms,P < 0.01). T2 was measurable in 66% of group A and 83% of group B patients. The heart/muscle signal intensity ratio in group A (0.45 ± 0.27) was lower than in group B (0.82 ± 0.33,P < 0.001) and the controls (1.15 ± 0.20,P < 0.001). The heart/muscle signal intensity ratio was measurable in 94% of the patients and demonstrated an inverse relationship with the serum ferritin levels(r = - 0.52, P<0.01). This study indicates that the heart/muscle ratio is a sensitive index of iron overload and it can be measured in the majority of patients, irrespective of tissue iron concentration, thereby offering an advantage over the use of T2 relaxation time. © 1998 Elsevier Science B.V. All rights reserved.     

Dynamic contrast-enhanced MRI using macromolecular contrast media for monitoring the response to isolated limb perfusion in experimental soft-tissue sarcomas

The objective of this study was to evaluate the potential of dynamic contrast-enhanced MRI for quantitative characterization of tumor microvessels and to assess the microvascular changes in response to isolated limb perfusion with TNF- and melphalan. Dynamic contrast-enhanced MRI was performed in an experimental cancer model, using a macromolecular contrast medium, albumin-(Gd-DTPA)₄₅. Small fragments of BN 175, a soft-tissue sarcoma, were implanted in 11 brown Norway (BN) rats. Animals were assigned randomly to a control (Haemaccel) or drug-treated group (TNF-/melphalan). MRI was performed at baseline and 24 h after ILP. The transendothelial permeability (K^PS) and the fractional plasma volume (fPV) were estimated from the kinetic analysis of MR data using a two-compartment bi-directional model. K^PS and fPV decreased significantly in the drug-treated group compared to baseline (p<0.05). In addition, K^PS post therapy was significantly lower (p<0.05) in the drug-treated group than in the control group. There was no significant difference in fPV between the drug-treated and the control group after therapy. Tumor microvascular changes in response to isolated limb perfusion can be determined after 24 h by dynamic contrast-enhanced MRI. The data obtained in this experimental model suggest possible applications in the clinical setting, using the appropriate MR contrast agents.     

Optimising the design of paramagnetic MRI contrast agents: influence of backbone substitution on the water exchange rate of Gd-DTPA derivatives

Among other factors influencing the residence time of the coordinated water (τ _M ) of paramagnetic contrast agents, the steric hindrance around the gadolinium ion seems to play a beneficial role. Such a crowding can be achieved by substituting the Gd-DTPA backbone on the C4 position. Several Gd-DTPA complexes carrying diverse groups at this position have thus been synthesised and characterised: Gd(S)-C₄-Me-DTPA, Gd(S)-C₄-n-Bu-DTPA, Gd(S)-C₄-iBu-DTPA, Gd(S)-C₄-iPr-DTPA, and Gd-C₄-diMe-DTPA. τ _M has been measured through the evolution of the water oxygen-17 transverse relaxation rate as a function of the temperature. The data show a reduction of τ _M of Gd(S)-C₄-Me-DTPA, Gd(S)-C₄-n-Bu-DTPA, Gd(S)-C₄-iBu-DTPA, Gd(S)-C₄-iPr-DTPA, and Gd-C₄-diMe-DTPA (τ _M ³¹⁰=91,82, 108,98, and 57 ns respectively, as compared to Gd-DTPA (τ _M ³¹⁰=143 ns)). At 310 K, the nuclear magnetic dispersion relaxation profiles of water protons are very similar for the five complexes which present longitudinal relaxivities slightly higher than those of Gd-DTPA. Regarding zinc transmetallation, C4-monosubstituted derivatives are more stable than Gd-DTPA. These results confirm that a judicious substitution of the DTPA skeleton allows for an acceleration of the coordinated water exchange rate. This observation can be useful for the design of vectorised contrast agents for molecular imaging.