Advances in imaging techniques to assess kidney fibrosis

Figures & data

Figure 1. The pathological foundation of imaging techniques to assess kidney fibrosis. BOLD-MRI: Blood oxygenation level-dependent MRI; ASL-MRI: Arterial spin labeling MRI; SE: strain elastography; SWE: shear wave elastography; MRE: magnetic resonance elastography; PAI: photoacoustic imaging; ECM: extracellular matrix; MTI: magnetization transfer imaging; DWI: diffusion weighted imaging; DTI: diffusion tensor imaging; IVIM: intravoxel incoherent motion imaging; DKI: diffusion kurtosis imaging. The increase and deposition of ECM lead to the increase of kidney stiffness and macromolecule content, meanwhile, decrease the tissue oxygenation and perfusion, restrict the diffusion of water molecules. This pathologic change is the foundation of different imaging techniques to assess kidney fibrosis.

Table 1. Features of noninvasive imaging techniques for assessing kidney fibrosis.

Method	Detection	index	Advantage	Disadvantage
SE	Tissue stiffness	Tissue mean elasticity	Simple to operate, cost effective	Not applied to assess native kidney
SWE	Tissue stiffness	SWV, Young’s modulus	Simple to operate, cost effective, apply to allografts and native kidneys	Influenced by tubular or interstitial pressure, tissue anisotropy and tissue perfusion
MRE	Tissue stiffness	renal shear stiffness	Faster acquisition sequence	Influenced by tissue perfusion, edema
DWI	Diffusion of water molecules	ADC	Simple to operate, get results quickly and easily	Influenced by the microcirculation perfusion and the blood flow of peritubular capillary
DTI	Diffusion of water molecules	FA	More sensitive and stable than ADC, can reflect the renal microstructural change	The detection process is interference by motion, such as respiratory movement
IVIM	Diffusion of water molecules	D, D*, f	Can separate the true water molecular diffusion	The detection process is more complicated and require higher signal-to-noise ratio
DKI	Diffusion of water molecules	K, D	Can reflect more complicated microstructural change	Lack of applications experiences in kidney fibrosis
BOLD-MRI	Tissue oxygenation	T2*, R2*	Can assess the tissue oxygenation noninvasively	Influenced by renal plasma flow and oxygen consumption. Cannot analysis the tissue hypoxia in detail
ASL-MRI	Tissue perfusion	cortical ASL perfusion; renal blood flow	Use the endogenous water of arterial blood as an endogenous tracer, can detect the cortical perfusion and renal blood flow	Lack of applications experiences in kidney fibrosis; cannot detect medullary blood flow; low signal-to-noise ratio and resolution
MTI	Macromolecule content	PSR, f	Can detect the macromolecule content in renal and quantify the degree of renal fibrosis to some extent; Few influenced by renal perfusion	Lack of applications experiences in human
PAI	The collagen content	the collagen content	Can quantify the collagen of kidney；can detect small vessels without contrast agent	Lack of applications experiences in human; insufficient measuring depth
Fluorescence microscopy	The collagen content	SHG	Can quantify the collagen of kidney；visual and dynamic observation of kidney fibrosis；highly sensitive, accurate and fast	Lack of applications experiences in human; need expensive and delicate instrumentations

SE: strain elastography; SWE: shear wave elastography; SWV: shear wave velocity; MRE: magnetic resonance elastography; DWI: diffusion weighted imaging; ADC: apparent diffusion coefficient; DTI: diffusion tensor imaging; FA: fractional anisotropy; IVIM: intravoxel incoherent motion imaging; D: true diffusivity; D*: pseudo diffusion coefficient; f: perfusion fraction; DKI: diffusion kurtosis imaging; K: the apparent diffusional kurtosis; D: the diffusion coefficient; BOLD-MRI: Blood oxygenation level-dependent MRI; T2*: the transverse relaxation time; R2*: the reciprocal of T2*; ASL-MRI: Arterial spin labeling MRI; MTI: magnetization transfer imaging; f: the bound pool fraction; PAI: photoacoustic imaging; SHG: second harmonic generation.

Table 2. Studies on noninvasive imaging techniques for assessing kidney fibrosis.

	Animal experiment	CKD	Renal allograft
SE	None	None	Tissue mean elasticity calculated from SE was negatively correlated with the degree of renal fibrosis [3]
SWE	SWE values had a positive correlation with kidney fibrosis in UUO model [4]	Kidney shear wave speed measured by ARFI was lower in patients with diabetic kidney disease or lower eGFR [5]; the mean Young’s modulus was found to be negatively correlated with eGFR [6]	kidney stiffness measured by TE was found significantly higher in renal allograft cortical interstitial fibrosis [7]
MRE	Shear stiffness measured by MRE increased with the progression of nephrocalcinosis in rat model [8]; renal medullary stiffness measured by MRE had a positive correlation with degree of fibrosis in pig model with renal artery stenosis [9]	renal stiffness values had a negative correlation with parameters of renal fibrosis in patients with glomerulonephritis and amyloid A amyloidosis [10]; the MRE values had a negative correlation with the interstitial extracellular matrix volume in patients with CKD [11];	Whole-kidney stiffness was positively associated with biopsy-derived fibrosis score and negatively associated with eGFR [12];
DWI	The ADC of kidney with an acute rejection was lower than kidney without rejection [13];	The renal ADC had a negative correlation with histological fibrosis score [14,15]	The ADC values of the patients with histologically proven evidence of acute rejection were lower than those with stable allograft function [16]
DTI	Cortex FA decreased in the early stage of renal fibrosis in rat models with diabetic nephropathy [17];	FA in the renal cortex and medulla had a significant negative correlation with glomerulosclerosis and tubulointerstitial fibrosis [18]	FA could detect allograft dysfunction early and had a negative correlation with the amount of renal fibrosis in patients after kidney transplantation [19]
IVIM	D, D*, and f values of the renal cortex and medulla decreased after obstruction in UUO model [20]	The values of f had a significantly negative correlation with interstitial fibrosis and tubular atrophy [21]	The values of f had a negative correlation with the time to recovery with respect to MRI and may predict the time to recovery in delayed graft function [22]
DKI	The mean D of cortex had a negative correlation with urea and alpha-SMA [23]	the renal parenchymal mean D values had a negative correlation with the histopathological fibrosis score, and the renal parenchymal mean K values had a positive correlation with histopathological fibrosis score [24];	None
BOLD-MRI	The T2* values were negatively correlated with the percentage of renal fibrotic area in a rabbit UUO model [25];	T2* was negatively correlated with fibrotic area [26]; the correlation between R2* and renal function was controversial	The cortical R2* values were positively associated with interstitial fibrosis in patients with allograft injury [27];
ASL-MRI	Mean cortical perfusion was higher in rats with chronic rejections than acute rejections, and the cortical renal blood flow was positively correlated with renal creatinine clearance [28]	The ASL perfusion decreased along with the exacerbation of fibrosis [29];	The combination of cortical ASL perfusion could effectively distinguish the allografts with subclinical pathology [30];
MTI	The renal fibrotic region had a higher pool size ratio [31,32]	None	None
PAI	2D PA imaging–based scores had a significant positive correlation with histological results [33]	None	None
Fluorescence microscopy	The SHG imaging found more collagen in the fibrotic kidney [34]; This HistoIndex platform could detect the collagen deposition of fibrotic kidney sensitively [35]	None	None

SE: strain elastography; SWE: shear wave elastography; ARFI: acoustic radiation force impulse; eGFR: estimated glomerular filtration rate; TE: transient elastography; MRE: magnetic resonance elastography; CKD: chronic kidney disease; DWI: diffusion weighted imaging; ADC: apparent diffusion coefficient; DTI: diffusion tensor imaging; FA: fractional anisotropy; IVIM: intravoxel incoherent motion imaging; DKI: diffusion kurtosis imaging; K: the apparent diffusional kurtosis; D: the diffusion coefficient; alpha-SMA: alpha-smooth muscle actin; BOLD-MRI: Blood oxygenation level-dependent MRI; T2*: the transverse relaxation time; R2*: the reciprocal of T2*; UUO: unilateral ureteral obstruction; R2*: the reciprocal of T2*; ASL-MRI: Arterial spin labeling MRI; MTI: magnetization transfer imaging; PAI: photoacoustic imaging; SHG: second harmonic generation.

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