Measurement of Murine Single‐Kidney Glomerular Filtration Rate Using Dynamic Contrast‐Enhanced MRI

Abstract

The proposed DCE-MRI method may be useful for reliable noninvasive measurements of single-kidney GFR and perfusion in mice. Magn Reson Med 79:2935-2943, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Photoacoustic Imaging of Nanoparticle Transport in the Kidneys at High Temporal Resolution

“…Taking advantage of strong NIR absorption of the well-defined Au 25 (SG) 18 nanocluster, photoacoustic (PA) imaging was used to visualize its transport in situ through the aorta to the renal parenchyma and its subsequent filtration into the renal pelvis at at emporal resolution down to 1s .H igh temporal and spatial resolution imaging of Au 25 (SG) 18 kidney elimination allowed the accurate quantification of the glomerular filtration rate (GFR) of individual kidneys in normal and pathological conditions, broadening the biomedical applications of engineered nanoparticles in preclinical kidney research. Taking advantage of strong NIR absorption of the well-defined Au 25 (SG) 18 nanocluster, photoacoustic (PA) imaging was used to visualize its transport in situ through the aorta to the renal parenchyma and its subsequent filtration into the renal pelvis at at emporal resolution down to 1s .H igh temporal and spatial resolution imaging of Au 25 (SG) 18 kidney elimination allowed the accurate quantification of the glomerular filtration rate (GFR) of individual kidneys in normal and pathological conditions, broadening the biomedical applications of engineered nanoparticles in preclinical kidney research.…”

“…[4] While significant progression has been made in the fundamental understanding of physiology on the nanoscale, one big challenge in the field is to continue improving the temporal resolution of noninvasive imaging of in vivo transport of engineered nanoparticles at the anatomic level. To address these challenges,w er eport that by using photoacoustic (PA) imaging, we can directly image the in vivo transport of Au 25 (SG) 18 nanoclusters through the aorta to the renal parenchyma and their subsequent filtration into the renal pelvis at atemporal resolution of 1s .The high-temporal and spatial information derived from the in vivo transport of Au 25 (SG) 18 in the different kidney compartments allows us to noninvasively quantify the glomerular filtration rate (GFR) of individual normal and injured kidneys within very first minute,w hich offers an ew imaging tool for not only interrogating kidney dysfunction in preclinical settings,b ut also advancing our understanding of nephrology on the nanoscale with higher temporal and spatial resolution. To address these challenges,w er eport that by using photoacoustic (PA) imaging, we can directly image the in vivo transport of Au 25 (SG) 18 nanoclusters through the aorta to the renal parenchyma and their subsequent filtration into the renal pelvis at atemporal resolution of 1s .The high-temporal and spatial information derived from the in vivo transport of Au 25 (SG) 18 in the different kidney compartments allows us to noninvasively quantify the glomerular filtration rate (GFR) of individual normal and injured kidneys within very first minute,w hich offers an ew imaging tool for not only interrogating kidney dysfunction in preclinical settings,b ut also advancing our understanding of nephrology on the nanoscale with higher temporal and spatial resolution.…”

“…[10] Owing to the over 20 %c ardiac blood output received in kidneys,P Ai maging has been used for noninvasive imaging of renal vasculatures,b lood perfusion, and injuries. We chose asingle laser wavelength of 800 nm to excite Au 25 (SG) 18 as it is close to the isosbestic point of the major endogenous chromophores deoxyhaemoglobin (Hb) and oxyhaemoglobin (HbO 2 )f or minimized respiration interference ( Figure 1A). We chose asingle laser wavelength of 800 nm to excite Au 25 (SG) 18 as it is close to the isosbestic point of the major endogenous chromophores deoxyhaemoglobin (Hb) and oxyhaemoglobin (HbO 2 )f or minimized respiration interference ( Figure 1A).…”

“…[11] However,this strong blood PA signal has also been ab arrier for visualizing the in vivo transport of engineered nanoparticles in the kidneys.T oa ddress this challenge,w e synthesized the well-defined glutathione-coated Au25 nanoclusters (Au 25 (SG) 18 ,S upporting Information, Figure S1), which is known to be highly renal clearable and has strong absorption in the near infrared (NIR) region ( Figure 1A). Furthermore,s ingle-wavelength excitation enabled the acquisition of images at ah igh temporal resolution (approximately 1s), which is essential for the quantification of GFR using imaging-based techniques.Prior to in vivo PA imaging, we tested the PA signal of aseries of Au 25 (SG) 18 solutions of different concentration in tissue-mimicking phantoms (Supporting Information, Figure S2) and the signal increase was found to linearly (R 2 = 0.99) correlate with the increase in Au 25 (SG) 18 concentration ( Figure 1B), making it straightforward to convert PA signal to concentration when analyzing PA images.S ince ah igh power pulsed laser was used to generate PA signals in vivo,t he photochemical stability of Au 25 (SG) 18 was also evaluated. Furthermore,s ingle-wavelength excitation enabled the acquisition of images at ah igh temporal resolution (approximately 1s), which is essential for the quantification of GFR using imaging-based techniques.Prior to in vivo PA imaging, we tested the PA signal of aseries of Au 25 (SG) 18 solutions of different concentration in tissue-mimicking phantoms (Supporting Information, Figure S2) and the signal increase was found to linearly (R 2 = 0.99) correlate with the increase in Au 25 (SG) 18 concentration ( Figure 1B), making it straightforward to convert PA signal to concentration when analyzing PA images.S ince ah igh power pulsed laser was used to generate PA signals in vivo,t he photochemical stability of Au 25 (SG) 18 was also evaluated.…”

“…We chose asingle laser wavelength of 800 nm to excite Au 25 (SG) 18 as it is close to the isosbestic point of the major endogenous chromophores deoxyhaemoglobin (Hb) and oxyhaemoglobin (HbO 2 )f or minimized respiration interference ( Figure 1A). While the NIR absorption of conventional organic dyes decreased by 27-72 %a fter 3min exposure to a808 nm diode laser (0.5 Wcm À2 power density), Au 25 (SG) 18 showed almost unchanged NIR absorption after the same laser irradiation (Supporting Information, Figure S3), due to the high chemical stability of the Au 25 nanocluster.Different concentrations of Au 25 (SG) 18 exhibited fairly stable PA signals during the same pulsed laser excitation used for in vivo imaging (Supporting Information, Figure S4). While the NIR absorption of conventional organic dyes decreased by 27-72 %a fter 3min exposure to a808 nm diode laser (0.5 Wcm À2 power density), Au 25 (SG) 18 showed almost unchanged NIR absorption after the same laser irradiation (Supporting Information, Figure S3), due to the high chemical stability of the Au 25 nanocluster.Different concentrations of Au 25 (SG) 18 exhibited fairly stable PA signals during the same pulsed laser excitation used for in vivo imaging (Supporting Information, Figure S4).…”