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Quantification of Mouse Renal Perfusion Using Arterial Spin Labeled MRI at 1 T

Posted Aug 31, 2017 Updated Apr 10, 2023
By Quyen N. Do PhD , Ananth J. Madhuranthakam PhD , Peter Bendel PhD , Robert E. Lenkinski PhD
9 min read

Rationale and Objectives

Quantitative measurement of renal perfusion in murine models provides important information on the organ physiology and disease states. The 1-T desktop magnetic resonance imaging has a small footprint and a self-contained fringe field. This resultant flexibility in siting makes the system ideal for preclinical imaging research. Our objective was to evaluate the capability of the 1-T desktop magnetic resonance imaging to measure mouse renal perfusion without the administration of exogenous contrast agents.

Materials and Methods

We implemented a flow-sensitive alternating inversion recovery (FAIR)-based arterial spin labeling sequence with a mouse volume coil on a 1-T desktop magnetic resonance scanner. The validity of the implementation was tested by comparing obtained renal perfusion results with literature values for normal mice and challenging the technique with mice treated with furosemide, a blood vessel vasoconstrictor drug.

Results

The measured cortical and medullary perfusions were quantified to be 402 ± 95 and 184 ± 52 mL/100 g/min, respectively, in agreement with literature values. The ratio of cortical to medullary renal blood flow was between 2 and 3 and was independent of the mouse weight. As expected, upon furosemide injection, a decrease (~50%) in cortical perfusion was observed in the mice population, at 1 hour post injection compared to baseline ( P < 0.0001), which returned to baseline after 24 hours ( P = 0.68).

Conclusions

We reported the successful application of FAIR-based arterial spin labeling for noncontrast perfusion measurement of mouse kidneys using a 1-T desktop scanner. The easy implementation of FAIR sequence on a 1-T desktop scanner offers the potential for longitudinal perfusion studies in limited access areas such as behind the barrier in mouse facilities and in multimodality preclinical imaging laboratories without the administration of exogenous contrast agents.

Introduction

The quantitative measurement of renal perfusion in murine models is important in preclinical research to assess both renal function and the effects of antiangiogenic therapies in models of renal cancer. Perfusion measurement gives information regarding organ performance, disease state, and understanding of inter- and intratumoral metabolic heterogeneity . Tumor blood flow has also been suggested as a predictive parameter in assessing the effects of the treatment of tumors with antiangiogenic therapy . Imaging techniques that are based on radioactive tracers like positron emission tomography (PET) and single-photon emission computed tomography have been used to assess perfusion. However, applications of these techniques, particularly for longitudinal monitoring of disease progression or treatment to response, are limited due to radiation exposure and invasiveness. A magnetic resonance imaging (MRI) technique using dynamic contrast enhancement provides high–spatial resolution perfusion study but requires the injection of a gadolinium (Gd)-based contrast agent. Reports of a link between the administration of Gd-based contrast agents and nephrogenic systemic fibrosis , along with recent studies on Gd deposition in the brain , do not make contrast-enhanced MRI ideal for perfusion imaging. Noninvasive perfusion MRI techniques will therefore logically gain importance in multiparametric MRI methods in cancer research.

Arterial spin labeled (ASL) MRI is a noninvasive technique that has been used to measure noncontrast perfusion . ASL uses radiofrequency pulses and magnetic field gradients to label the inflowing spins of blood water molecules and measures their accumulation in the tissue of interest. ASL MRI can be broadly classified into two categories: pulsed ASL and continuous ASL. Continuous ASL can provide a higher signal-to-noise ratio (SNR) but requires external hardware that can be challenging to implement on standard scanners. Recent developments such as pseudocontinuous ASL can be performed on standard scanners without the need for additional hardware , but this technique requires a specific location to label the inflowing blood, which can be difficult to achieve in small animal imaging . Alternatively, the pulsed ASL technique using flow-sensitive alternating inversion recovery (FAIR) globally inverts all the blood spins outside the imaging slab, avoiding the challenges with labeling location, and is easy to implement on standard scanners for small animal imaging .

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Materials and Methods

Experimental Design

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FAIR Imaging Protocol

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Figure 1, Schematic of the FAIR-based ASL sequence as implemented with a mouse volume coil on a 1-T Desktop magnetic resonance scanner. The 180° inversion pulse was alternated between slice-selective (control) and slab-selective (label) by changing the slice-selection gradient strength. A spoiled gradient echo with a centric view ordering was used for data acquisition. RF, radiofrequency; TI, inversion time.

Figure 2, Signal change occurring with different inversion times in axial images of a mouse using the flow-sensitive alternating inversion recovery sequence. An inversion time of 1200 ms allows the visualization of renal perfusion without significant influence from strong signals arising from blood vessels while still providing a sufficient signal-to-noise ratio.

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Flow Quantification

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RBF=λ(SSel−Snonsel)2α∗TI∗SrefeTIT1 R

B

F

=

λ

(

S

S

e

l

−

S

nonsel

)

2

α

∗

T

I

∗

S

r

e

f

e

T

I

T

1

where λ is the tissue-blood partition coefficient, assumed to be 1.0 mL/g ; S is the signal for nonselective ( S nonsel ) and selective ( S sel ) ASL images, and the reference proton density image ( S ref ); TI is the inversion time (1.2 seconds); T 1 is the longitudinal relaxation time of blood, assumed to be 1.4 seconds at 1 T ; and α is the inversion efficiency, assumed to be 1.0 .

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Image Analysis

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Results

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Figure 3, The 1-T desktop magnetic resonance imaging can provide both anatomic and functional images of mouse kidneys in vivo. (a) T 2 -weighted fast spin echo image of mouse kidney shown in prone position. Renal substructures (c and m) are indicated. (b) Slice-selective (control) and slab-selective (label) images of mouse kidney acquired by the FAIR sequence. (c) Flow-sensitive alternating inversion recovery perfusion image, obtained by taking the difference between the control and label images, averaged across 36 pairs. The abdominal aorta (indicated by the arrow) has the highest blood flow. (d) Quantitative renal blood flow map in kidneys providing a cortical perfusion value of 390 ± 60 mL/100 g/min (red ROI) and medullary perfusion of 170 ± 60 mL/100 g/min (white ROI) in this mouse. C, cortex; m, medulla; ROI, region of interest. (Color version of figure is available online.)

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Figure 4, Our results show the direct relationship between the RBF and the weight of the mouse (a) . The standard deviation was calculated from the individual regions of interest in each mouse. The renal cortical and medullary perfusions were quantified to be about 402 ± 95 and 184 ± 52 (mL/100 g/min), respectively, across the mice. The ratio between the cortical and medullary RBF (black diamond) is independent of the mice weight and stays between 2 and 3 (b) .

TABLE 1

Means and Standard Deviations of Cortical and Medullary Blood Flow of Group 1 Mice, Measured Using the Flow-sensitive Alternating Inversion Recovery-Arterial Spin Labeling Technique on a 1-T Desktop Magnetic Resonance Scanner

Mouse Weight (g) Medullary Perfusion (mL/100 g/min) Cortical Perfusion (mL/100 g/min) 19.8 110 ± 54 241 ± 78 20.1 132 ± 64 301 ± 52 20.7 179 ± 38 357 ± 77 21.9 141 ± 53 295 ± 68 22.1 181 ± 60 356 ± 73 23.4 168 ± 59 392 ± 60 30.4 133 ± 75 336 ± 42 33.1 189 ± 141 472 ± 85 36.2 289 ± 119 548 ± 56 43.6 244 ± 100 561 ± 85 20.0 169 ± 57 399 ± 58 19.5 132 ± 45 380 ± 54 28.3 232 ± 60 449 ± 50 30.0 222 ± 40 417 ± 55 29.6 250 ± 58 535 ± 63

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Figure 5, Quantitative perfusion maps show a decrease in kidney perfusion after the injection of furosemide, a vasoconstrictor drug. After clearance of furosemide in 24 hours, renal perfusion returned to normal values, similar to preinjection. PI, post injection.

Figure 6, The flow-sensitive alternating inversion recovery technique implemented on the 1-T magnetic resonance imaging is sensitive to perfusion changes. The quantitative cortical blood flow of a particular mouse (30 g) decreases after the administration of furosemide (8 mg/kg IP). Perfusion values to the left of the arrow are preinjection; those to the right of the arrow are post injection.

Figure 7, Means and standard deviations of cortical blood flow before and after the administration of furosemide (8 mg/kg intraperitoneal) in mice ( n = 6). The cortical blood flow decreased significantly following the administration of furosemide, measured at 1 hour compared to baseline (one-sided P value <0.0001). The renal perfusion returned to baseline values after 24 hours PI (one-sided P value = 0.68). PI, post injection.

TABLE 2

Means and Standard Deviations of Cortical Blood Flow (mL/100 g/min) of Group 2 Mice, Before (Preinjection) and After Treatment with Furosemide (1, 4, 8, and 24 hours PI)

Mouse Weight (g) Preinjection 1 h PI 4 h PI 8 h PI 24 h PI 28.0 \* 486 ± 54 161 ± 41 — — — 26.2 \* 131 ± 35 109 ± 32 — — — 27.3 \* 349 ± 71 103 ± 24 — — — 34.0 \* 414 ± 71 168 ± 35 — — — 27.3 \* 220 ± 54 147 ± 38 — — — 26.9 \* 331 ± 49 179 ± 62 — — — 41.6 446 ± 72 191 ± 75 334 ± 50 338 ± 35 503 ± 81 20.0 400 ± 66 182 ± 53 302 ± 90 364 ± 58 344 ± 41 19.5 368 ± 70 172 ± 63 283 ± 37 281 ± 67 446 ± 71 28.3 373 ± 44 260 ± 84 447 ± 84 384 ± 58 424 ± 41 30.0 460 ± 93 196 ± 61 352 ± 73 410 ± 72 461 ± 54 29.6 624 ± 88 214 ± 46 444 ± 61 539 ± 55 558 ± 68

PI, post injection.

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Discussion

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Conclusions

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Academic Radiology, Volume 24, Issue 9
Journals General Radiology
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