Volume‐targeted and whole‐heart coronary magnetic resonance angiography using an intravascular contrast agent

Purpose

To compare volume‐targeted and whole‐heart coronary magnetic resonance angiography (MRA) after the administration of an intravascular contrast agent.

Materials and Methods

Six healthy adult subjects underwent a navigator‐gated and ‐corrected (NAV) free breathing volume‐targeted cardiac‐triggered inversion recovery (IR) 3D steady‐state free precession (SSFP) coronary MRA sequence (t‐CMRA) (spatial resolution = 1 × 1 × 3 mm³) and high spatial resolution IR 3D SSFP whole‐heart coronary MRA (WH‐CMRA) (spatial resolution = 1 × 1 × 2 mm³) after the administration of an intravascular contrast agent B‐22956. Subjective and objective image quality parameters including maximal visible vessel length, vessel sharpness, and visibility of coronary side branches were evaluated for both t‐CMRA and WH‐CMRA.

Results

No significant differences (P = NS) in image quality were observed between contrast‐enhanced t‐CMRA and WH‐CMRA. However, using an intravascular contrast agent, significantly longer vessel segments were measured on WH‐CMRA vs. t‐CMRA (right coronary artery [RCA] 13.5 ± 0.7 cm vs. 12.5 ± 0.2 cm; P < 0.05; and left circumflex coronary artery [LCX] 11.9 ± 2.2 cm vs. 6.9 ± 2.4 cm; P < 0.05). Significantly more side branches (13.3 ± 1.2 vs. 8.7 ± 1.2; P < 0.05) were visible for the left anterior descending coronary artery (LAD) on WH‐CMRA vs. t‐CMRA. Scanning time and navigator efficiency were similar for both techniques (t‐CMRA: 6.05 min; 49% vs. WH‐CMRA: 5.51 min; 54%, both P = NS).

Conclusion

Both WH‐CMRA and t‐CMRA using SSFP are useful techniques for coronary MRA after the injection of an intravascular blood‐pool agent. However, the vessel conspicuity for high spatial resolution WH‐CMRA is not inferior to t‐CMRA, while visible vessel length and the number of visible smaller‐diameter vessels and side‐branches are improved. J. Magn. Reson. Imaging 2009;30:1191–1196. © 2009 Wiley‐Liss, Inc.     

Intra‐thoracic blood volume measurement by contrast magnetic resonance imaging

The intra‐thoracic blood volume (ITBV) is a cardiovascular parameter related to the cardiac preload and left ventricular function. Its assessment is, therefore, important for diagnosis and follow‐up of several cardiovascular dysfunctions. Nowadays, the ITBV can be accurately measured only by invasive indicator dilution techniques, which require a double catheterization of the patient. In this study, a novel technique is presented for ITBV assessment by dynamic magnetic resonance imaging after intravenous injection of a small bolus of gadolinium chelate. The dose was chosen on the basis of in vitro calibration. The bolus first pass is detected from a simultaneous dynamic image series of the right and left ventricles. Two indicator dilution curves are derived and used to inspect the transpulmonary dilution system. Various mathematical models for the interpretation of the measured indicator dilution curves are compared. The ITBV is assessed as the product of the transpulmonary mean transit time of the indicator and the cardiac output, obtained by phase contrast magnetic resonance angiography. In vitro measurements showed a correlation coefficient larger than 0.99 and preliminary tests with volunteers proved the feasibility of the method, opening new possibilities for noninvasive quantitative cardiovascular diagnostics. Magn Reson Med 61:344–353, 2009. © 2009 Wiley‐Liss, Inc.     

Quantitative magnetic resonance imaging of perfusion using magnetic labeling of water proton spins within the detection slice

A technique for noninvasive quantitative magnetic resonance imaging of perfusion is presented. It relies on using endogenous water as a freely diffusible tracer. Tissue water proton spins are magnetically labeled by slice-selective inversion, and longitudinal relaxation within the slice is detected using a fast gradient echo magnetic resonance imaging technique. Due to blood flow, nonexcited spins are washed into the slice resulting in an acceleration of the longitudinal relaxation process. Incorporating this phenomenon into the Bloch equation yields an expression that allows quantification of perfusion on the basis of a slice-selective and a nonselective inversion recovery experiment. Based on this technique, quantitative parameter maps of the regional cerebral blood flow (rCBF) were obtained from eight rats. Evaluation of regions of interest within the cerebral hemispheres yielded an average rCBF value of 104 ± 21 ml/min/100 g, which increased to 219 ± 30 ml/min/100 g during hypercapnia. The measured rCBF values are in good agreement with previously reported literature values.     

Measurement of kinetic parameters in skeletal muscle by magnetic resonance imaging with an intravascular agent.

The purpose of this work was to investigate the use of an intravascular contrast agent to determine perfusion kinetics in skeletal muscle. A two-compartment kinetic model was used to represent the flux of contrast agent between the intravascular space and extravascular extracellular space (EES). The relationship between the image signal-to-noise ratio (SNR) and errors in estimating permeability surface area product (Ktrans), interstitial volume (ve), and plasma volume (vp) for linear and nonlinear curve-fitting methods was estimated from Monte Carlo simulations. Similar results were obtained for both methods. For an image SNR of 60, the estimated errors in these parameters were 10%, 22%, and 17%, respectively. In vivo experiments were conducted in rabbits to examine physiological differences between these parameters in the soleus (SOL) and tibialis anterior (TA) muscles in the hind limb. Values for Ktrans were significantly higher in the SOL (3.2+/-0.9 vs. 2.0+/-0.5x10(-3) min-1), as were values for vp (3.4+/-0.8 vs. 2.1+/-0.7%). Differences in ve for the two muscles (8.7+/-2.2 vs. 8.5+/-1.6%) were not found to be significant. These results demonstrate that relevant physiological metrics can be calculated in skeletal muscle using MRI with an intravascular contrast agent.     

In vivo quantification of regional myocardial blood flow: validity of the fast-exchange approximation for intravascular T1 contrast agent and long inversion time.

In the present study we investigated the effects of water exchange between intra- and extravascular compartments on absolute quantification of regional myocardial blood flow (rMBF) using a saturation-recovery sequence with a rather long inversion time (TI, 176 ms) and a T1-shortening intravascular contrast agent (CMD-A2-Gd-DOTA). Data were acquired in normal and ischemically injured pigs, with radiolabeled microsphere flow measurements used as the gold standard. Five water exchange rates (fast, 6 Hz, 3 Hz, 1 Hz, and no exchange) were tested. The results demonstrate that the fast-exchange approximation may be appropriate for rMBF quantification using the described experimental setting. Relaxation rate change (DeltaR1) analysis improved the accuracy of the analysis of rMBF compared to the MR signal. In conclusion, the current protocol could provide sufficient accuracy for estimating rMBF assuming fast exchange and a linear relationship between signal and tissue concentration when quantification of precontrast T1 is not an option.     

Measurement of capillary permeability to macromolecules by dynamic magnetic resonance imaging: A quantitative noninvasive technique

A simple, linear kinetic model has been developed for the noninvasive assessment of capillary permeability to macromolecules in the rat by dynamic magnetic resonance imaging using albumin-Gd-DTPA. Data required by the model are signal intensity responses from a target tissue and a venous structure such as inferior vena cava before and after bolus intravenous injection of albumin-Gd-DTPA. Additional requirements include an early temporal resolution of approximately one image/min and a blood sample for hematocrit. The model does not require measurement of albumin-Gd-DTPA concentration in either arterial or venous blood. Pilot experiments suggest that this technique is adequate for estimation of the fractional leak rate of macromolecules from plasma to interstitial water as well as tissue plasma volume, the product of which yields a measure of the permeability surface area product of the tissue if the extraction fraction is modest (<0.2). The technique may be generally applicable to the study of abnormal capillary permeability in humans as well as animals.     

Determination of regional blood volume and intra-extracapillary water exchange in human myocardium using Feruglose: First clinical results in patients with coronary artery disease.

The aim of this pilot study in humans was to investigate the effect of an intravascular contrast agent (CA) on relaxation rate in myocardium (R(1,myo)) in the steady state. The dependence of R(1,myo) on R(1,blood) was characterized and compared with a theoretical model which allowed determination of the intra- extracapillary water proton exchange frequency (f = 0.48 s(-1)) and the intracapillary blood volume (RBV = 12.9 %). A linear response range of DeltaR(1,myo) on DeltaR(1,blood) was estimated which in future studies will allow the determination of RBV with intravascular CA.     

Mapping myocardial perfusion with an intravascular MR contrast agent: robustness of deconvolution methods at various blood flows.

Evaluation of quantitative parameters such as regional myocardial blood flow (rMBF), blood volume (rMBV), and mean transit time (rMTT) by MRI is gaining acceptance for clinical applications, but still lacks robust postprocessing methods for map generation. Moreover, robustness should be preserved over the full range of myocardial flows and volumes. Using experimental data from an isolated pig heart preparation, synthetic MR kinetics were generated and four deconvolution approaches were evaluated. These methods were then applied to the first-pass T(1) images of the isolated pig heart using an intravascular contrast agent and rMBF, rMBV and rMTT maps were generated. In both synthetic and experimental data, the fit between calculated and original data reached equally good results with the four techniques. rMBV was the only parameter estimated correctly in numerical experiments. Moreover, using the algebraic method ARMA, abnormal regions were well delineated on rMBV maps. At high flows, rMBF was underestimated at the experimental noise level. Finally, rMTT maps appeared noisy and highly unreliable, especially at high flows. In conclusion, over the myocardial flow range, i.e., 0-400 ml/min/100g, rMBF identification was biased in presence of noise, whereas rMBV was correctly identified. Thus, rMBV mapping could be a fast and robust way to detect abnormal myocardial regions.     

Gadolinium-DTPA-dextran: a macromolecular MR blood pool contrast agent

RATIONALE AND OBJECTIVES: Magnetic resonance (MR) imaging blood pool agents offer numerous advantages for vascular and tumor imaging. The purpose of this study was to test gadolinium-diethylenetriaminepentaacetate-dextran ([Gd]DTPA-dextran) as a new water soluble macromolecular blood pool agent for MR imaging. MATERIALS AND METHODS: [Gd]DTPA-dextran (187 gadolinium atoms per dextran, molecular weight 165 kD, diameter 17.6 nm) was synthesized. Fifteen anesthetized New Zealand White rabbits with thigh VX2 tumors were scanned in a knee coil at 1.5T. Coronal 3D MR angiographic sequences were obtained before and at several time points up to 72 hours after the intravenous bolus injection of [Gd]DTPA-dextran providing gadolinium at either 0.05 (n = 4) or 0.1 mmol/kg (n = 8) or [Gd]DTPA-bismethylamide (BMA) providing gadolinium at 0.1 mmol/kg (n = 3). Time enhancement curves for aorta, cava, and tumor rim were compared by univariate General Linear Model. RESULTS: Contrast enhancement of cava and aorta relative to a water phantom were significantly greater at all time points after either dose of [Gd]DTPA-dextran than after [Gd]DTPA-BMA (P < 0.01). Tumor rim enhancement was less intense for either dose of [Gd]DTPA-dextran at peak than for [Gd]DTPA-BMA (P < 0.05). Tumor rim enhancement with both doses of [Gd]DTPA-dextran became equivalent to that of [Gd]DTPA-BMA at one hour and was greater at 24 hours (P < 0.05). CONCLUSION: [Gd]DTPA-dextran is a new macromolecular MR contrast agent that can be synthesized to carry a high density of gadolinium atoms without intra-molecular cross-linking. It provides significantly greater vascular residence time than a conventional gadolinium chelate and shows promise for MR blood pool imaging.     

Improving MR quantification of regional blood volume with intravascular T1 contrast agents: Accuracy,precision, and water exchange

The goal of this work was to develop a comprehensive understanding of the relationship between vascular proton exchange rates and the accuracy and precision of tissue blood volume estimates using intravascular T₁ contrast agents. Using computer simulations, the effects of vascular proton exchange and experimental pulse sequence parameters on measurement accuracy were quantified. T₁ and signal measurements made in a rat model implanted with R3230 mammary adenocarcinoma tumors demonstrated that the theoretical findings are biologically relevant; data demonstrated that over-simplified exchange models may result in measures of tumor, muscle, and liver blood volume fractions that depend on experimental parameters such as the vascular contrast concentration. As a solution to the measurement of blood volume in tissues with exchange that is unknown, methods that minimize exchange rate dependence were examined. Simulations that estimated both the accuracy and precision of such methods indicated that both the inversion recovery and the transverse-spoiled gradient echo methods using a “noexchange” model provide the best trade-off between accuracy and precision.     

Acute dural venous sinus thrombosis without brain parenchymal abnormality: assessment with cerebral blood volume using dynamic susceptibility contrast magnetic resonance imaging

We report results applying the dynamic susceptibility contrast (DSC) magnetic resonance (MR) technique to a patient with dural venous sinus thrombosis (DVST) of the right transverse-sigmoid sinus without brain parenchymal abnormality. The DSC-MR technique clearly demonstrated increased regional cerebral blood volume of the right temporo-parieto-occipital region adjacent to a right transverse-sigmoid sinus thrombosis in a patient with DVST without cerebral edema or hemorrhage.     

Contribution of Sinerem® used as blood-pool contrast agent: Detection of cerebral blood volume changes during apnea in the rabbit

The authors suggest that ultra-small paramagnetic iron oxide (USPIO) particles used as blood pool contrast agents may increase the sensitivity of midfield MRI (i.e., less than 1.5 Tesla) to physiological variations in cerebral blood volume. This hypothesis was tested on a rabbit model of apnea which increases pCO₂ and cerebral blood volume. Using Sinerem® as the USPIO at a blood concentration of 60 μmol iron/kg body weight, an 8% T₂*-weighted signal decrease could be observed at 1.0 T with 25–33% increase in pCO₂. Comparatively, in the absence of USPIO, T₂*-weighted signal dropped only 4% during apnea and after mild hyperoxygenation beforehand, due to increased deoxyhemoglobin content. These preliminary data suggest that USPIOs could play an important role in functional MRI at midfield strength, by sensitizing the signal to cerebral blood volume changes.     

Evaluation of methemoglobin as an autologous intravascular MRI contrast agent

Methemoglobin (MetHb) was evaluated as an intravascular paramagnetic contrast agent. Methemoglobin formation was induced by 4-dimethylaminophenol (4-DMAP), causing a reduction in blood T₂* in vitro. The 4-DMAP generated metHb with a time constant of 62 s. A 4-DMAP bolus did not decrease measurably the signal intensity in the in vivo rabbit kidney in the first pass. At steady state, a MetHb concentration of 24.8 ± 2.3% resulted in a signal decrease of 9.2 ± 2.6% in the kidney. Methemoglobin is an effective vascular T₂* relaxation agent, but the formation of MetHb by 4-DMAP is too slow for first-pass imaging. A more effective conversion agent resulting in a bolus of at least 25% MetHb within 5 s would result in a detectable first-pass signal and a viable contrast technique.     

Quantitative rapid steady state T1 magnetic resonance imaging for cerebral blood volume mapping in mice: Lengthened measurement time window with intraperitoneal Gd‐DOTA injection

This work demonstrates how the rapid steady state T₁ MRI technique for cerebral blood volume fraction (BVf) quantification can be used with intraperitoneal Gd‐DOTA injections in mice at 4.7 T. The peak signal amplitude after intravenous administration (0.7 mmol/kg) and the steady state signal amplitude reached 15 min after intraperitoneal administration (6 mmol/kg) in the same mice lead to equivalent BVf measures in the order of 0.02 in the brain. The resulting time window for BVf quantification is ≈30 min and allows for cerebral BVf mapping with increased spatial resolution or signal‐to‐noise ratio, or for monitoring functional BVf changes. A cerebral BVf increase of up to 25% induced by the vasodilator acetazolamide was observed, validating the vascular origin of the signal. The noninvasive and quantitative rapid steady state T₁ technique can be used in serial studies to evaluate new drugs or disease models, such as antiangiogenic therapies in tumors. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Reliability of in vivo determination of forearm muscle volume using 3.0 T magnetic resonance imaging

Purpose:

To apply magnetic resonance imaging (MRI) as a tool for quantifying muscle volume of forearm muscles feasibility and reliability of volume estimation of the flexor carpi ulnaris (FCU) and the extensor carpi ulnaris (ECU).

Materials and Methods:

Forearms of 10 subjects were scanned twice. Muscle volumes were calculated from manual outlines on axial slices, slice thickness, and the number of slices. Observer agreement and repeatability were estimated using intraclass correlation, coefficient of variation, and the smallest detectable difference.

Results:

The average volume of the FCU and ECU was 31.0 mL (SD 11.5 mL) and 16.4 mL (SD 7.7 mL), respectively. Intraclass correlation coefficients of the volumes were all above 0.99 and the coefficient of variation varied between 5.7% and 0.8%. The smallest detectable difference corresponded to ≈7% of muscle volume.

Conclusion:

MRI muscle volume measurement of forearm muscles is feasible, reproducible, and allows for longitudinal studies where expected responsiveness exceeds 7%. J. Magn. Reson. Imaging 2010;31:1252–1255. © 2010 Wiley‐Liss, Inc.     

Iron oxide nanoparticles as magnetic resonance contrast agent for tumor imaging via folate receptor-targeted delivery

RATIONALE AND OBJECTIVE: Targeted delivery is a highly desirable strategy for diagnostic imaging because of enhanced efficacy and reduced dosage/toxicity. Receptor-targeting was used to deliver contrast-producing superparamagnetic iron oxide (IO) nanoparticle to receptor-expressing tumors for in vivo magnetic resonance (MR) imaging. MATERIALS AND METHODS: Nanometer-sized, dextran-coated (maghemite) IO particles were prepared by a precipitation method. They were tethered with N-hydroxysuccinimide-folate and fluorescence isothiocyanate (FITC). For in vitro study of delivery specificity and efficiency, KB cells, a human nasopharyngeal epidermal carcinoma cell line expressing surface receptors for folic acid, were used as positive targets, and A549 cells, a human lung carcinoma cell line which lacks folate receptors, were used as negative control targets. In vivo MR images were obtained using mouse models with subcutaneous tumor xenografts grown from implanted KB cells. RESULTS: Internalization of nanoparticles into targeted cells only occurred when IO was conjugated to folate and when the folate receptors are available and accessible on the cells. The endocytosis was efficient and rapid, as 97.5% KB cells cultured with folate-FITC-IO showed FITC uptake after 1 hour of incubation. In in vivo MR imaging, an average intensity decrease of 38% was observed from precontrast to postcontrast images of the tumor, which was about three times the intensity decrease observed at a non-tumor-bearing muscle. CONCLUSION: Successful in vivo MR imaging of folate receptor-expressing tumors targeted by IO nanoparticles was demonstrated for the first time.     

Contrast agent dose effects in cerebral dynamic susceptibility contrast magnetic resonance perfusion imaging

Purpose

To study the contrast agent dose sensitivity of hemodynamic parameters derived from brain dynamic susceptibility contrast MRI (DSC‐MRI).

Materials and Methods

Sequential DSC‐MRI (1.5T gradient‐echo echo‐planar imaging using an echo time of 61–64 msec) was performed using contrast agent doses of 0.1 and 0.2 mmol/kg delivered at a fixed rate of 5.0 mL/second in 12 normal subjects and 12 stroke patients.

Results

1) Arterial signal showed the expected doubling in relaxation response (ΔR2*) to dose doubling. 2) The brain signal showed a less than doubled ΔR2* response to dose doubling. 3) The 0.2 mmol/kg dose studies subtly underestimated cerebral blood volume (CBV) and cerebral blood flow (CBF) relative to the 0.1 mmol/kg studies. 4) In the range of low CBV and CBF, the 0.2 mmol/kg studies overestimated the CBV and CBF compared with the 0.1 mmol/kg studies. 5) The 0.1 mmol/kg studies reported larger ischemic volumes in stroke.

Conclusion

Subtle but statistically significant dose sensitivities were found. Therefore, it is advisable to carefully control the contrast agent dose when DSC‐MRI is used in clinical trials. The study also suggests that a 0.1 mmol/kg dose is adequate for hemodynamic measurements. J. Magn. Reson. Imaging 2009;29:52–64. © 2008 Wiley‐Liss, Inc.     

Comparison of two volumetric techniques for estimating liver volume using magnetic resonance imaging

PURPOSE: To compare the conventional technique of manual planimetry with the point counting technique for estimating liver volume from magnetic resonance imaging (MRI) data. MATERIALS AND METHODS: This study comprised abdominal MR examinations of 38 consecutive patients. Evaluation of the images showed that liver size appeared normal in 27 patients and increased in 11. Liver volume was estimated using the techniques of planimetry and point counting. Both techniques were used in combination with the Cavalieri method of modern design stereology. A systematic slice sampling procedure was performed to estimate liver volumes using both volumetric techniques. The point counting technique was optimized by altering the point spacing of the grid. The agreement between the two techniques was found. Measurement repeatability of both volumetric techniques was also evaluated. RESULTS: Both techniques allowed the same degree of optimization through the procedure of systematic section sampling. The application of a point spacing of 2.5 cm reduced the time measurement by a factor of 3.5 in relation with the time needed with planimetry. An excellent agreement was observed between the two volumetric techniques with mean differences (+/-SD) of 2.4 +/- 41.6 cm(3) and 8.5 +/- 49.8 cm(3) for the patients presenting normal and increased liver sizes, respectively. Both techniques were highly reproducible. CONCLUSION: The point counting technique could be considered a more efficient approach than planimetry for estimating liver volume from MRI, due to its speed and simplicity.