Quantification of renal perfusion abnormalities using an intravascular contrast agent (part 2): results in animals and humans with renal artery stenosis.

The interrelation between the morphologic degree of renal artery stenosis and changes in parenchymal perfusion is assessed using an intravascular contrast agent. In seven adult foxhounds, different degrees of renal artery stenosis were created with an inflatable clamp implanted around the renal artery. Dynamic susceptibility-weighted gradient-echo imaging was used to measure signal-time curves in the renal artery and the renal parenchyma during administration of 1.5 mg/kg BW of an intravascular ultrasmall particle iron oxide (USPIO) contrast agent. From the dynamic series, regional renal blood volume (rRBV), regional renal blood flow (rRBF), and mean transit time (MTT) were calculated. The morphologic degree of stenosis was measured in the steady state using a high-resolution 3D contrast-enhanced (CE) MR angiography (MRA) sequence (voxel size = 0.7 x 0.7 x 1 mm(3)). Five patients with renoparenchymal damage due to long-standing renal artery stenosis were evaluated. In the animal stenosis model, cortical perfusion remained unchanged for degrees of renal artery stenosis up to 80%. With degrees of stenoses > 80%, cortical perfusion dropped to 151 +/- 54 ml/100 g of tissue per minute as compared to a baseline of 513 +/- 76 ml/100 g/min. In the patients, a substantial difference in the cortical perfusion of more than 200 +/- 40 ml/100 g/min between the normal and the ischemic kidneys was found. The results show that quantitative renal perfusion measurements in combination with 3D-CE-MRA allow the functional significance of a renal artery stenosis to be determined in a single MR exam. Differentiation between renovascular and renoparenchymal disease thus becomes feasible.     

Quantification of renal perfusion and function on a voxel-by-voxel basis: a feasibility study.

The feasibility of a voxel-by-voxel deconvolution analysis of T(1)-weighted DCE data in the human kidney and its potential for obtaining quantification of perfusion and filtration was investigated. Measurements were performed on 14 normal humans and 1 transplant at 1.5 T using a Turboflash sequence. Signal time-courses were converted to tracer concentrations and deconvolved with an aorta AIF. Parametric maps of relative renal blood flow (rRBF), relative renal volume of distribution (rRVD), relative mean transit time (rMTT), and whole cortex extraction fraction (E) were obtained from the impulse response functions. For the normals average cortical rRBF, rRVD, rMTT, and E were 1.6 mL/min/mL (SD 0.8), 0.4 mL/mL (SD 0.1), 17s (SD 7), and 22.6% (SD 6.1), respectively. A gradual voxelwise rRBF increase is found from the center of two infarction zones toward the edges. Voxel IRFs showed more detail on the nefron substructure than ROI IRFs. In conclusion, quantitative voxelwise perfusion mapping based on deconvolved T(1)-DCE renal data is feasible, but absolute quantification requires inflow correction. rRBF maps and quantitative values are sufficiently sensitive to detect perfusion abnormality in pathologic areas, but further research is necessary to separate perfusion from extraction and to characterize the different compartments of the nephron on the (sub)voxel level.     

Pulmonary MR perfusion at 3.0 Tesla using a blood pool contrast agent: Initial results in a swine model

PURPOSE: To prospectively evaluate the technical feasibility of a highly accelerated pulmonary MR perfusion protocol at 3.0T using a blood pool contrast agent in a swine model. MATERIALS AND METHODS: Twelve pigs underwent time-resolved pulmonary MR angiography (MRA) on a 3.0T MR system under anesthesia and controlled mechanical ventilation. After intravenous injection of 0.05 mmol/kg of Gadomer-17 at 4 mL/second, a fast time-resolved MRA sequence with temporal echo-sharing (three segmented k-space) and highly accelerated parallel acquisition was used to acquire 3D data sets with an in-plane resolution of 1 x 1 mm(2) (slice thickness = 6 mm) and temporal resolution of one second. Image quality was evaluated independently by two radiologists, and quantitative analysis of perfusion parameters was performed using pre-released perfusion software. RESULTS: All studies were identified by both readers as having diagnostic image quality (range = 2-3, median = 3) and there was excellent interobserver agreement (kappa = 0.89; 95% CI = 0.83, 0.95). A quantitative analysis of perfusion indices was performed, with excellent overall goodness-of-fit (chi(2) value = 1.4, degree of freedom (DF) = 1). Successfully derived perfusion parameters included the time to peak (TTP, 5.1 +/- 0.7 second), mean transit time (MTT, 6.6 +/- 0.9 second), maximal signal intensity (MSI, 1051.2 +/- 718.9 arbitrary units [A.U.]), and maximal upslope of the curve (MUS, 375.9 +/- 263.4 A.U./second). CONCLUSION: 3.0T pulmonary MR perfusion using a blood pool contrast agent in a swine model is feasible. The higher available signal-to-noise ratio (SNR) at 3.0T and the high T1 relaxivity of Gadomer-17 effectively support highly accelerated parallel acquisition, and improve the performance of time-resolved pulmonary MRA.     

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.     

On the theoretical basis of perfusion measurements by dynamic susceptibility contrast MRI.

A quantitative analysis was undertaken to calibrate the perfusion quantification technique based on tracking the first pass of a bolus of a blood pool contrast agent. A complete simulation of the bolus passage, of the associated changes in the T2 and T2* signals, and of the data processing was performed using the tracer dilution theory, an analytical theory of the MR signal from living tissues and numerical simulations. The noise was excluded in the simulation in order to analyze the ultimate accuracy of the method. It is demonstrated that the relationship between the contrast agent concentration and the associated changes in the transverse relaxation rate shows essentially different forms in studied tissue and in the reference artery. This effect results in systematic deviations of the measured blood flow, blood volume, and the residue function obtained with conventional processing from their true values. The error depends on the microvascular composition, the properties of the contrast agent, and the weights of the various compartments in the total signal. The results show that dynamic susceptibility contrast MRI can reach the goal of absolute perfusion quantification only with additional input from measurements of the microvascular architecture. Alternatively, the method can be used to provide such information if the perfusion is quantified by another modality.     

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.     

Dynamic contrast-enhanced quantitative perfusion measurement of the brain using T1-weighted MRI at 3T

PURPOSE: To develop a method for the measurement of brain perfusion based on dynamic contrast-enhanced T(1)-weighted MR imaging. MATERIALS AND METHODS: Dynamic imaging of the first pass of a bolus of a paramagnetic contrast agent was performed using a 3T whole-body magnet and a T(1)-weighted fast field echo sequence. The input function was obtained from the internal carotid artery. An initial T(1) measurement was performed in order to convert the MR signal to concentration of the contrast agent. Pixelwise and region of interest (ROI)-based calculation of cerebral perfusion (CBF) was performed using Tikhonov's procedure of deconvolution. Seven patients with acute optic neuritis and two patients with acute stroke were investigated. RESULTS: The mean perfusion value for ROIs in gray matter was 62 mL/100g/min and 21 mL/100g/min in white matter in patients with acute optic neuritis. The perfusion inside the infarct core was 9 mL/100g/min in one of the stroke patients. The other stroke patient had postischemic hyperperfusion and CBF was 140 mL/100g/min. CONCLUSION: Absolute values of brain perfusion can be obtained using dynamic contrast-enhanced MRI. These values correspond to expected values from established PET methods. Furthermore, at 3T pixelwise calculation can be performed, allowing construction of CBF maps.     

Advantages of frequency-domain modeling in dynamic-susceptibility contrast magnetic resonance cerebral blood flow quantification.

In dynamic-susceptibility contrast magnetic resonance perfusion imaging, the cerebral blood flow (CBF) is estimated from the tissue residue function obtained through deconvolution of the contrast concentration functions. However, the reliability of CBF estimates obtained by deconvolution is sensitive to various distortions including high-frequency noise amplification. The frequency-domain Fourier transform-based and the time-domain singular-value decomposition-based (SVD) algorithms both have biases introduced into their CBF estimates when noise stability criteria are applied or when contrast recirculation is present. The recovery of the desired signal components from amid these distortions by modeling the residue function in the frequency domain is demonstrated. The basic advantages and applicability of the frequency-domain modeling concept are explored through a simple frequency-domain Lorentzian model (FDLM); with results compared to standard SVD-based approaches. The performance of the FDLM method is model dependent, well representing residue functions in the exponential family while less accurately representing other functions.     

Quantification of bolus-tracking MRI: Improved characterization of the tissue residue function using Tikhonov regularization.

Quantification of cerebral blood flow (CBF) and the tissue residue function (R) using bolus-tracking MRI requires deconvolution of the arterial input function (AIF). Currently, the most commonly used deconvolution method is singular value decomposition (SVD), which has been shown to produce accurate estimations of CBF. However, this method introduces unwanted oscillations in the time course of R, and there are situations in which the actual shape is of interest (e.g., in calculating flow heterogeneity and assessing bolus dispersion). In such cases, the conventional SVD method may no longer be suitable, and an alternative approach may be required. This work describes the implementation of Tikhonov regularization with the L-curve criterion to quantify CBF and obtain a better characterization of R. The methodology is tested on simulated and patient data, and the results are compared to those found using the conventional SVD approach. Although both methods produce similar CBF values, the deconvolved R shape obtained using SVD is dominated by oscillations and fails to characterize the shape in the presence of dispersion. On the other hand, the use of the proposed regularization method improves the characterization of the tissue residue function.     

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.     

Improved three-dimensional free-breathing coronary magnetic resonance angiography using gadocoletic acid (B-22956) for intravascular contrast enhancement

PURPOSE: To evaluate gadocoletic acid (B-22956), a gadolinium-based paramagnetic blood pool agent, for contrast-enhanced coronary magnetic resonance angiography (MRA) in a Phase I clinical trial, and to compare the findings with those obtained using a standard noncontrast T2 preparation sequence. MATERIALS AND METHODS: The left coronary system was imaged in 12 healthy volunteers before B-22956 application and 5 (N = 11) and 45 (N = 7) minutes after application of 0.075 mmol/kg of body weight (BW) of B-22956. Additionally, imaging of the right coronary system was performed 23 minutes after B-22956 application (N = 6). A three-dimensional gradient echo sequence with T2 preparation (precontrast) or inversion recovery (IR) pulse (postcontrast) with real-time navigator correction was used. Assessment of the left and right coronary systems was performed qualitatively (a 4-point visual score for image quality) and quantitatively in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel sharpness, visible vessel length, maximal luminal diameter, and the number of visible side branches. RESULTS: Significant (P < 0.01) increases in SNR (+42%) and CNR (+86%) were noted five minutes after B-22956 application, compared to precontrast T2 preparation values. A significant increase in CNR (+40%, P < 0.05) was also noted 45 minutes postcontrast. Vessels (left anterior descending artery (LAD), left coronary circumflex (LCx), and right coronary artery (RCA)) were also significantly (P < 0.05) sharper on postcontrast images. Significant increases in vessel length were noted for the LAD (P < 0.05) and LCx and RCA (both P < 0.01), while significantly more side branches were noted for the LAD and RCA (both P < 0.05) when compared to precontrast T2 preparation values. CONCLUSION: The use of the intravascular contrast agent B-22956 substantially improves both objective and subjective parameters of image quality on high-resolution three-dimensional coronary MRA. The increase in SNR, CNR, and vessel sharpness minimizes current limitations of coronary artery visualization with high-resolution coronary MRA.     

T1-weighted functional imaging based on a contrast agent in presurgical mapping

Purpose

To assess the applicability of T1‐weighted images in the presence of a contrast agent for functional mapping free of susceptibility artifacts, in comparison to the blood oxygenation level‐dependent (BOLD) imaging.

Materials and Methods

Six patients and five control subjects were scanned using BOLD and T1‐weighted functional imaging, in the presence of a Gd‐DTPA contrast‐agent (TOFICA). In the control group, low‐ and high‐resolution BOLD images were performed. Functional stimuli included motor and language activations.

Results

Both BOLD and TOFICA methods resulted in activations in the expected anatomical regions. The TOFICA mapping gave less distributed and with higher percent signal changes in comparison with the BOLD images. Gd‐DTPA remained almost constant in the blood for at least 15 min post injection. In one patient with surgical clips, no signal was detected in the left cerebral hemisphere using BOLD imaging, but activation could be mapped using the TOFICA method.

Conclusion

T1‐weighted imaging in the presence of a contrast agent can be used for functional mapping. This method is insensitive to susceptibility artifacts, and is therefore advantageous in the evaluation of presurgical cases and in areas of the brain close to cavities in which the BOLD method cannot reliably be applied. J. Magn. Reson. Imaging 2008;28:1245–1250. © 2008 Wiley‐Liss, Inc.     

Quantification of the effect of water exchange in dynamic contrast MRI perfusion measurements in the brain and heart.

Measurement of myocardial and brain perfusion when using exogenous contrast agents (CAs) such as gadolinium-DTPA (Gd-DTPA) and MRI is affected by the diffusion of water between compartments. This water exchange may have an impact on signal enhancement, or, equivalently, on the longitudinal relaxation rate, and could therefore cause a systematic error in the calculation of perfusion (F) or the perfusion-related parameter, the unidirectional influx constant over the capillary membranes (K(i)). The aim of this study was to quantify the effect of water exchange on estimated perfusion (F or K(i)) by using a realistic simulation. These results were verified by in vivo studies of the heart and brain in humans. The conclusion is that water exchange between the vascular and extravascular extracellular space has no effect on K(i) estimation in the myocardium when a normal dose of Gd-DTPA is used. Water exchange can have a significant effect on perfusion estimation (F) in the brain when using Gd-DTPA, where it acts as an intravascular contrast agent.     

MR susceptibility weighted imaging (SWI) complements conventional contrast enhanced T1 weighted MRI in characterizing brain abnormalities of Sturge-Weber Syndrome

PURPOSE: To evaluate the efficacy of susceptibility weighted imaging (SWI) in comparison to standard T1 weighted postgadolinium contrast (T1-Gd) MRI in patients with Sturge-Weber Syndrome (SWS). MATERIALS AND METHODS: Twelve children (mean age, 5.6 years) with the diagnosis of SWS and unilateral hemispheric involvement were recruited prospectively and examined with high resolution three dimensional SWI and conventional T1-Gd. Both SWI and T1-Gd images were evaluated using a four-grade scoring system according to six types of imaging findings (enlargement of transmedullary veins, periventricular veins, and choroid plexus, as well as leptomeningeal abnormality, cortical gyriform abnormality, and gray matter/white matter junctional abnormality). The scores of SWI versus T1-Gd images were then compared for each type of abnormality. RESULTS: SWI was superior to T1-Gd in identifying the enlarged transmedullary veins (P = 0.0020), abnormal periventricular veins (P = 0.0078), cortical gyriform abnormalities (P = 0.0020), and gray matter/white matter junction abnormalities (P = 0.0078). Conversely, T1-Gd was better than SWI in identifying enlarged choroid plexus (P = 0.0050) and leptomeningeal abnormalities (P = 0.0050). CONCLUSION: SWI can provide useful and unique information complementary to conventional contrast enhanced T1 weighted MRI for characterizing SWS. Therefore, SWI should be integrated into routine clinical MRI protocols for suspected SWS.     

The impact of partial-volume effects in dynamic susceptibility contrast magnetic resonance perfusion imaging

PURPOSE: To demonstrate the degree of the cerebral blood flow (CBF) estimation bias that could arise from distortion of the arterial input function (AIF) as a result of partial-volume effects (PVEs) in dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI). MATERIALS AND METHODS: A model of the volume fraction an artery occupies in a voxel was devised, and a mathematical relationship between the amount of PVE and the measured baseline MR signal intensity was derived. Based on this model, simulation studies were performed to assess the impact of PVE on CBF. Furthermore, the effectiveness of linear PVE compensation approaches on the concentration function was investigated. RESULTS: Simulation results showed a nonlinear relationship between PVE and the resulting CBF measurement error. In addition to AIF underestimation, PVE also causes distortions of AIF frequency characteristics, leading to CBF errors varying with mean transit time (MTT). An uncorrected AIF measured at a voxel with a partial-volume fraction of 相似文献