Measurement of bulk liver perfusion: Assessment of agreement between ASL and caval subtraction phase-contrast MRI at 9.4T
Manil Chouhan1, Rajiv Ramasawmy2, Alan Bainbridge3, Adrienne Campbell-Washburn2, Jack Wells2, Shonit Punwani1, Rajeshwar Mookerjee4, Simon Walker-Samuel2, Mark Lythgoe2, and Stuart Taylor1

1UCL Centre for Medical Imaging, University College London, London, United Kingdom, 2UCL Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom, 3Department of Medical Physics, University College London Hospitals NHS Trust, London, United Kingdom, 4UCL Institute for Liver and Digestive Health, University College London, London, United Kingdom

Synopsis

Non-invasive preclinical liver perfusion measurements could be used to develop biomarkers and assess new treatments for liver disease and primary/secondary malignant liver lesions. ASL can provide regional hepatic perfusion maps, and in this study we compare FAIR ASL tissue perfusion measurements with caval subtraction phase-contrast MRI, a validated method for measuring total liver blood flow, to demonstrate ASL overestimation but encouraging agreement between both methods.

Purpose

Non-invasive preclinical liver perfusion measurements could be used to develop biomarkers and assess new treatments for liver disease(1) and primary/secondary malignant liver lesions(2). Arterial spin labelling (ASL) has been applied in other organs(3,4) but has been challenging to implement in the liver, mainly because of its dual hepatic arterial (HA) and portal venous (PV) vascular supply, and susceptibility to respiratory motion.

Previously we have demonstrated that a Look-Locker Flow-Sensitive Alternating Inversion Recovery (FAIR) ASL technique is suitable for pre-clinical liver perfusion measurements(5) and compared these with phase-contrast (PC) MRI measurements of the portal vein (PV) in rats(6). However, the PV only contributes approximately 75% of liver perfusion and as such the comparative PCMRI measurement excludes the contribution of the HA. Caval subtraction PCMRI is a novel, validated method for assessment of total liver blood flow (TLBF) using measurements of bulk flow in the inferior vena cava(7). In this study we combine ASL with caval subtraction PCMRI at 9.4T to assess agreement between methods within subjects.

Methods

Scans were performed on a 9.4T Agilent 20 cm horizontal-bore system (Agilent Technologies, USA), using a 72 mm birdcage coil (RAPID Technologies, Germany). Healthy Sprague-Dawley rats (n=9) were anaesthetised with isoflurane, and their respiratory rate, ECG and temperature monitored (SA Instruments, USA).

Two-dimensional cine PCMRI

Axial and angled coronal gradient echo images were used to plan caval PCMRI studies. Cardiac and respiratory-triggered 2D cine PCMRI was performed (TR/TE=10/1.2ms, α=10°, 2 mm slice thickness, 192x192 matrix, FOV 40x40mm2, 10-15 cardiac cycle phases, Venc=33 and 66 cm/s for proximal and distal IVC flows). ROIs were positioned manually on each vessel for each frame of the cardiac cycle and flow quantification was performed using in-house developed Matlab code. TLBF was estimated by subtracting proximal IVC flow (above renal but below hepatic venous inlets) from distal IVC flow (above hepatic venous inlets, but below the IVC-right atrial junction). Estimated TLBF measurements were normalised to explanted liver weight.

ASL acquistion

An axial slice that enabled good visualisation of hepatic parenchyma was selected from respiratory-gated anatomical images. A FAIR Look-Locker ASL sequence was used using an end-expiration triggered segmented acquisition with a spoiled gradient-echo readout (FOV 60x60 mm2, 128x128 matrix, 2 mm slice thickness, TE=1.18 ms, TI=110 ms, TRRF=2.3 ms, αLL=8˚, TRI=13 seconds, 50 inversion recovery readouts, 15 minute acquisition time). Images were processed using in-house developed Matlab code and ASL perfusion maps were calculated using the Belle model(3), as described previously(5). Three identically sized circular ROIs were placed on the hepatic parenchyma avoiding major vascular structures and extra-hepatic tissues. ASL perfusion estimates were based on averages obtained from the three ROIs (figure 1).

Results

Mean ASL bulk liver perfusion (351.1±26.4 ml/min/100g) was less than mean caval subtraction PCRMI estimated TLBF (459.9±40.5 ml/min/100g). The mean difference (bias) between ASL and PCMRI measurements of bulk liver perfusion was 144.8 ml/min/100g, suggesting ASL underestimation. The Bland-Altman 95% Limits of Agreement (BA 95% LoA) were ±166.9 ml/min/100g, with significant positive correlations between measurements (r=0.7162, p=0.0150, figure 2). The coefficient of variation was similar for both ASL (25.1%) and caval subtraction PCMRI TLBF (26.4%).

Discussion

Previously, we have demonstrated the feasibility of measuring localised liver perfusion using FAIR ASL(5) and reported expected overestimation of FAIR ASL bulk liver perfusion relative to weight normalised PCMRI bulk PV flow(6). While ASL perfusion maps are a mixture of both the arterial and portal venous contribution, in this study we have demonstrated a tendency for FAIR ASL bulk liver perfusion to underestimate perfusion relative to caval subtraction PCMRI estimated TLBF. Nonetheless, allowing for the systematic bias, the BA 95% LoAs and strong correlation are both encouraging for the use of FAIR ASL for the assessment of regional hepatic perfusion. The underestimation of FAIR ASL may be due to imperfect labelling due to the large coil loading(8). Our use of caval subtraction PCMRI to validate FAIR ASL is a useful application of this method and will be a valuable tool for the assessment of pre-clinical models of hepatic disease.

Conclusion

FAIR ASL tends to overestimate hepatic perfusion, but demonstrates encouraging agreement with caval subtraction PCMRI.

Acknowledgements

This work was supported by a Wellcome Trust Clinical Research Training Fellowship (grant WT092186), a Wellcome Trust Senior Research Fellowship (grant WT100247MA), an MRC Capacity Building Studentship and the British Heart Foundation, King’s College London and UCL Comprehensive Cancer Imaging Centre CR-UK & EPSRC, in association with the DoH (England).

References

1. Van Beers BE, Leconte I, Materne R, Smith AM, Jamart J, Horsmans Y. Hepatic perfusion parameters in chronic liver disease: dynamic CT measurements correlated with disease severity. AJR Am J Roentgenol 2001;176(3):667-673.

2. Jackson A, Haroon H, Zhu XP, Li KL, Thacker NA, Jayson G. Breath-hold perfusion and permeability mapping of hepatic malignancies using magnetic resonance imaging and a first-pass leakage profile model. NMR in biomedicine 2002;15(2):164-173.

3. Belle V, Kahler E, Waller C, et al. In vivo quantitative mapping of cardiac perfusion in rats using a noninvasive MR spin-labeling method. Journal of magnetic resonance imaging : JMRI 1998;8(6):1240-1245.

4. Golay X, Hendrikse J, Lim TC. Perfusion imaging using arterial spin labeling. Topics in magnetic resonance imaging : TMRI 2004;15(1):10-27.

5. Ramasawmy R, Campbell-Washburn AE, Wells JA, et al. Hepatic arterial spin labelling MRI: an initial evaluation in mice. NMR in biomedicine 2015;28(2):272-280.

6. Chouhan M, Ramasawmy R, Campbell-Washburn A, et al. Measurement of bulk liver perfusion: initial assessment of agreement between ASL and phase-contrast MRI at 9.4T. Proc Intl Soc Mag Reson Med. Volume 21; 2013. p. 2190.

7. Chouhan M, Mookerjee R, Bainbridge A, et al. Caval subtraction 2D phase-contrast MRI to measure total liver and hepatic arterial blood flow: preclinical validation and initial clinical translation. Radiology 2015 (accepted, in submission).

8. Wells JA, Siow B, Lythgoe MF, Thomas DL. The importance of RF bandwidth for effective tagging in pulsed arterial spin labeling MRI at 9.4T. NMR in biomedicine 2012;25(10):1139-1143.

Figures

Figure 1: ASL perfusion maps and ROI placement

Anatomical images (a) were used to select a slice for quantification. The segmented area for quantitative analysis is demonstrated by the dashed white line. T1 maps were generated with consensus ROI placement (blue circles, b).


Figure 2: Analysis of agreement between FAIR ASL bulk perfusion and caval subtraction PCMRI total liver blood flow

Data from healthy rats, demonstrated ±166.9 ml/min/100g Bland-Altman 95% Limits of Agreement (a). A strong and significant correlation between methods was demonstrated (b).




Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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