Contrast-enhanced ultrasound

Prospective research

N = 10 (20 kidneys).

Healthy volunteers

Evaluation of different techniques of contrast-enhanced phase inversion ultrasound to visualize renal perfusion.

Comparison of contrast-enhanced phase-inversion ultrasound with B-mode or Doppler mode techniques.

CEUS was performed on 20 kidneys with different mechanical index levels and frame rate.

Analysis was done using software algorithm for time-resolved perfusion and compared to single-image analysis.

High mechanical index to destroy microbubbles and low frame rate (0.5 images/second) were optimal to depict renal perfusion.

‘’Renal perfusion can be visualized using contrast-enhanced phase-inversion ultrasound. For depiction of bigger vessels, it is equal to B-mode ultrasound or Doppler mode techniques; however, it is superior for visualization of renal parenchymal perfusion’’.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367302/

Healthy controls (n=12), median age = 49.5 yrs

Age and sex matched

Assess renal perfusion in scleroderma patients (renal damage is common in scleroderma).

Sonovue was infused and destroyed using Siemens Sequoia.

ROI: renal parenchyma,  interlobular artery and renal pyramid

ROI were analyzed using quantitative contrast software CUSQ 1.4.

Time to maximal (TmE), maximal enhancement (mE) and maximal enhancement relative to maximal enhancement of the interlobular artery (mE%A) were calculated  for each ROIs.

Renal perfusion could be assessed in scleroderma patients using CEUS.

‘’ There was a linear correlation between the TmE in the parenchyma and the GFR assessed by MDRD that was close to stastical significance. (P=0.8)”.

https://ccforum.biomedcentral.com/articles/10.1186/cc12817

12 patients at high risk of AKI planned for cardiac surgery.

Inclusion : Age above 70 years, pre-existing renal impairment (preoperative pCr (>120 umol/L), NYHA Class ¾ or LVEF <35%, valvular surgery, redo cardiac surgery or insulin-dependent type 2 diabetes mellitus.

‘’Establishe CEU’s feasibility, safety, reproductibility and potential diagnostic value in the assessment of renal cortical perfusion in the peri-operative period in cardiac surgery patients.

CEUS using IU22 ultrasound system and  Snovue was done before the operation, on ICU arrival and the day following the admission.

Hemodynamic parameters were obtained peri-operatively.

A dedicated softward (Sonotumor) was used to export video sequences and two independent radiologist blinded to patient and time performed the analysis.

The software generates a perfusion index (PI) which is proportional to perfusion at a ROI.

‘’All 36 renal CEUS studies, including 24 in the immediate post-operative period could be performed and were well tolerated’’”.

‘’Correlation between readers PI was excellent.’’

‘’IN patients at risk of AKI, CEUS-derived parameters suggest a decrease in renal cortical perfusion in the 24 hours following cardiac surgery’’.

(Further studies with larger sample size are required to establish whether there is a correlation between changes in microvascular cortical flow

And markers of renal function)) pour la discussion/resultat.

10.4329/wjr.v9.i1.10

N=50

CEUS using sulphur hexafluoride-filled microbubble contrast agent was performed   over a 8 year period to rule out vascular causes of ARF.

Detection rate of vascular abnormalities were calculated and compared to the detection rate of color Doppler ultrasound.

‘’ The detection rate of infarction  was significantly higher (p=0.0002) compared to color Doppler ultrasonography.

‘’CEUS showed high detection rate of renal perfusion abnormalities in patients with ARF’’.

Yan, Z. H. A. N. G., Yinghong, X. U. E., & Donghui, J. I. (2022). The Evaluation of Renal Blood Perfusion after Atherosclerotic Renal Artery Stenosis by rTCEUS. IMAGING SCIENCE AND PHOTOCHEMISTRY, 40(3), 464.

N = 31

TIC  was derived before and after PTRAS and perfusion parameters were analyzed.

‘’ The peak intensity (PI) and rising slope (S) of the curve after PTRAS were significantly higher than those before PTRAS (P<0.05), while the peak time (TTP) and mean transit time (MTT) were significantly lower than those before PTRAS (P<0.05)’’.

Other parameters (i.e ΔAUC) did not correlate.

‘’Parameters obtained by rTCEUS have a great value in evaluating the changes of renal blood flow in patients with severe renal artery stenosis after PTRAS’’.

Friedersdorff et al. (2022)

https://www.mdpi.com/2077-0383/11/3/791/htm

Prospectiveresearch

Healthy kidney donors

N= 30 (60 kidneys)

Identify relationship between kidney function and perfusion determined by CEUS.

Comparison of CEUS perfusion parameters with established methods of kidney function evaluation (DTPA and eGFR).

DTPA was determined for  the measurement of the total kidney function, while MAG3 scintigraphy was used for the assessment of the split renal function.

CEUS was performed using Sonovue one day before nephrectomy.

Kidney perfusion parameters was quantified with a TIC using VueBox postprocessing tool.

‘’Mean signal intensity (MeanLin) had the strongest correlation ..wtih EGF and total kidney function)’’.

‘’Signal intensity parameters as opposed to time dependent parameters  had the strongest correlation, which were similar for preoperative total kidney function, preoperative split kidney function and postoperative kidney.

No correlation was made between DTPA (reference method) and MeanLIn. However, when stratified by weight, a significant correlation is detected (r=-0.409, p =0.001).

Results suggest a possible association between CEUS intensity parameters and kidney function in normal-weight individuals.

More research is required.

10.3390/diagnostics12051293

N= 10

Median age = 39 yrs

Using Sonovue and using a Philips iU22 ultrasound machine (with contrast-specific software

5destruction/reperfusion sequences were captured. One phase association was performed to derive perfusion parameters.

Analysis was performed using VueBox^® Gastrointestinal (GI)I Perfusion Package. VueBox yielded time-intensity curves and parametric images.

Repeatability was evaluated using intra-class correlation (ICC).

‘’Interoperator repeatability was excellent for all perfusion parameters’’.

‘’Time-based variable (mTT) has a good repeatability (ICC: 0.71) and iis likely the most reliable measure … to assess changes in perfusion over time.  The large intra-individual variability in intensity-based measures (AI) seen in some patients  (ICC : 0.5) suggest that parameter may not be suitable for this purpose’’.

10.1155/2020/7145728

Exclusion criteria; Patients with nephrectomy, renal tuberculosis, renal aneurysm and anomalous origin of the renal artery.

N= 63 (total 122 renal arteries)

Mean age = 57.3 +/- 6.7 yrs

.

Digital substraction angiography  (DSA) was used as the gold standard and comparator

Sonovue was used.

Accuracy of the grading was assessed using the area under the receiver operating characteristic (ROC) curves and compared between groups.

Stenosed renal arteries were grade 1 to 4 using the stenosis rate equation (1- (X/R) x 100%.

X: minimum diameter of stenosed region

R: maximum diameter of stenosed region.

Sensitivity, specificity, accuracy, PPV, NPV were

88.9%, 87.8%, 88.5%, 93.5%, and 80.0%, respectively. Higher than DUS.

The kappa consistency was 0.749 (good consistency = 0.61-0.80).

‘CEUS can enhance the flow visualization of renal artery stenosis, and it showed a good consistency with the gold standard DSA. As a noninvasive, nonradiative, nontoxic, accurate, and cost-effective technique, CEUS may represent the method of choice in grading renal artery stenosis.’

doi:10.3389/fcvm.2022.721201

Prospective observational study

Inclusion criteria;

1.Patients who were diagnosed as unilateral or bilateral RAS via CEUS and  latter by DSA.  2. Patients who did not undergo CTA, MRA or DSA before CEUS.

Exclusion criteria;  incomplete clinical data

N= 40 (0.6 M, 0.4, F), 80 renal arteries

Median age (60.98 +/- 17.81)

Average BMI  24.20 +/- 3.61 kg/m’2

Evaluate  the accuracy, role and limitations of  CEUS in the investigation of suspected RAS and its limitations.

CEUS using a Samsung RS80A ultrasound scanner and  Sonovue as the CA was performed  to assess the the renal artery followed by DSA.

ROC curves were derived  and  the  diagnosis performance of the presence and dregree of stenosis using CEUS was compared to DSA results.

CEUS  was accurate to diagnose the presence (sensitivity= 96.4%, specificity = 95.8%) and the degree of severity of RAS and was consistent with DSA.

Misdiagnosis were usually in mild to moderate stenosis cases.

The addition of CEUS to hemodynamic indicators (i.e. Doppler ultrasound) can help improve the diagnosis of RAS.

Operator’s standardized examination (i.e. duration of investigation and  professional training) was shown to be an important predictor  for the accuracy of the diagnosis of RAS.

https://link.springer.com/article/10.1007/s00261-022-03457-w

Mean age = 64.4 +/- 18.0  yrs

‘’Compare the sensitivity and specificity of CEUS for diagnosis of RAS in CKD patients, using DSA and CTA as the gold standards.’’

Assess the value of CEUS in the follow-up post renal artery revascularization.

CEUS was done using Sonovue as a CA to evaluate stenotic renal arteries; then,  DSA or CTA was performed to verify the accuracy of CEUS in the diagnosis of renal artery stenosis.

CEUS was performed for a median follow-up time of 5.0  month.

Results showed that CEUS had a good consistency (kappa = 0.776), was accurate, specific and specific. In addition, no difference were found in the accuracy of CEUS to diagnose Tayasu RAS compared to atherosclerotic RAS.

Furthermore, they concluded that CEUS ‘’is a reliable tool for follow-up surveillance after renal artery revascularization’’.

‘’ CEUS examination is a credible alternative for diagnosing moderate and severe RAS in patients with CKD’’

Inclusion criteria included met the diagnostic criteria for sepsis and ≥ 18-years-old .

Exclusion criteria :  1) kidney transplantation, renal benign/malignant tumor, and vascular disease before admission 2) severe heart failure within 72h 3) patient gave up halfway, 4) pregnant women, lactating women, patient with mental disabilities 5) poor results of CEUS.

Assess the usefulness of CEUS and other indicators of renal function (i.e serum creatinijne and blood urea nitrogen (BUN)) in the early diagnosis of septic AKI.

Patients were divided into an AKI group (n=24) and a non-AKI group based on renal function and urine output in the 48h following sepsis diagnosis.

On the 7^th day, the non-AKI group was subdivided again into an AKI and non-AKI subgroup based on the same criteria.

CEUS  was performed using Sonazoid and an offline software was used to form a TIC and CEUS quantitative parameters.

Differences of the indicators in various subgroups were compared using X² test.

Peak intensity and wash in slope were lower in the AKI group than those in the non-AKI group (P< 0.05.

Sensitivities of CEUS parameters WIS and PI (100% and 100%) were higher than  the sensitivity of Scr (56.76%), but they had lower specificities (71.70% and 75.47%) than Scr (100%) for the diagnosis of septic AKI.

‘’The combination of Scr, PI and WIS can improve the diagnostic accuracy of septic AKI.’’

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313752/

Exclusion criteria;
≤18 yrs, contraindication to CA (history of cardiac shunt, respiratory disorders or hypersentivitiy).

N = 48  (25% prerenal, 71% intrinsic, 2% post renal, 1% intrinsic and postrenal).

Mean age = 60.65 ± 16.14 years

To evaluate CEUS-driven parameters as  predictors for renal outcome including KDIGO AKI stage,  initiation of renal replacement therapy (RRT),AKI recovery and CKD progression) in patients with AKI.

All patients underwent CEUS with a Philipps Iu22 at the occurrence of AKI

Sonovue was used.

3 similar size region of interest  (ROI) from the renal cortex and medulla were chosen. Time-intensity curves (TIC) were extracted using computer assisted program. For every ROI, the analysis was repeated 3 times and the mean value was used for comparison.  ROC was used to evaluate performance of various perfusion parameters.

‘’None of the TIC parameters  showed stastically significant difference between patients with intrinsic, prerenal or renal AKI’’”

Primary outcome: Initiation of RTT was precited by cortical MTT (OR= 1.07) and RT (1.20).

Secondary outcome = AKI recovery was predicted by cortical WIS (OR= 76.23) and medullary PI (OR=125) and CKD prediction was predicted by medullary PI (O.78 and AUC.

‘’By  evaluating renal microperfusion, CEUX may be used as a supplemental tool to estimate severity of renal dysfunction and to predict renal outcomes after AKI.

https://pubmed.ncbi.nlm.nih.gov/29036800/

Prospective observational study

CKD patients (proven by pathology ), n=275

Healthy adults, n=30

‘’ Assess the severity of renal pathology in patients with chronic kidney disease (CKD) using contrast-enhanced ultrasonography (US)’’.

.

CEUS was performed and US parameters were derived.

Patients were classified in categories of various CKD severity based on renal pathology findings.

Analysis was performed using logistic correlation and ROC curves.

“ Peak intensity was associated independently with  the severity f renal pathology in patients with CKD’’.

PI less than 13.87 dB has a sensitivity and specificity of 72.5% and 64.0, respectively.

There may be a potential role for CEUS in the evaluation of disease severity, follow-up and treatment guidance of CKD.

Kidney allograft recipients

N= 63 (31 F, 32 M)

Recipients were further divided into an early good function (EGF) and delayed graft function (DFG).

The DFG subgroup was further diagnosed with biopsy into the cause of the DFG either acute rejection (AR) or acute tubular necrosis (ATN).

Mean age = 49 +/-/ 16 yrs.

Evaluate the usefulness of CE-US  in the early post-transplant  (72-120 hours post-op) .assessment of graft perfusion and the determination of the cause of delayed graft function (DFG).

Ultrasound examinations including B-mode, Color-Doppler and pulse wave were performed. In addition, RI measurements were performed at the level of the segmental arteries

Afterwards, patients underwent CE-US with Sonovue (2.4 mL) as the CA and local perfusion was assessed using a TIC.

TIC of the ROIs were compared to the hemodynamic flow parameters.

‘’ A delay of contrast medium inflow strongly indicates DFG’’.

‘’There was significantly longer inflow time of the contrast medium to the cortex and renal pyramids in patients with AR than in ATN recipients’’.

‘’US-CE  may be a valuable tool in the determination of the cause of DGF’’.

Patient who underwent kidney transplantation

N = 180

Investigate the ability of CEUS to detect graft parenchyma perfusion disturbances (GPPD) in the postoperative period.

Compare the visualization of ischemic foci by CEUS with real-time US (B mode) with color and power Doppler (US-CD/PD) and B-flow ultrasound.

Patients were investigated using B+US-CD/PD/B-flow and CEUS in the immediate postoperative period and follow-up examinations were carried out up to 6 months postoperatively.

Number and size of ischemic foci were compared between the two acquisition protocols.

CE-US revealed more GPPDS and was more precise in detecting them.  In addition, ischemic foci were better visualized using CE-US compared to B+US-CD/PD/B-flow,

The authors recommend CE-US as routine diagnostic procedure in the early postoperative period following kidney transplantation.

Prospective observational study

Patien/t who underwent a kidney transplantation.  (deceased/living donor ; 86 %/11%)

N= 79

Age at transplantation : 52.1 +/- 14.4 yrs

DFG = 12.5%, acute rejection 10.1%

‘’Describe the natural history of cortical capillary blood flow (CCBF) over time under diverse conditions of kidney transplant, to explore the influence of donor conditions and recipients events, and to determine the capacity of CCBF for predicting renal function in the medium term’’.

Real-time contrast enhanced sonography (RT-CES) was performed in all patient after 48h, 5-7 days, and 1, 3 and 12 months post-transplantation.

At first, B-mode sonography and Doppler scan were performed.

Afterwards, CEUS was done using sulphur hexafluoride/Sonovue. Initial infusion was performed at 4 mL1min and optimal contrast visualization was achiev ed at 30-60 sec.

Quantification of renal cortical perfusion was done with CUSQ 1.4.

3 ROI: 2 in the renal cortex proximal to transducerren and 1 in the  cortex contralateral

The CCBF of each patient was calculated as the mean of the 3 selected ROIs.

CCBF was significantly lower at 48h and day 7 when compared to 1 and 3 months.

Over the first year,brain-death donor age and rejection episode had an inverse relationship with the CCBF.

Compared to brain-death donors, living donors had higher mean CCFF levels at each examination point.

‘’ RT-CES is a non-invasive tool that can quantify and iteratively estimate cortical microcirculation’’.

‘’The first week is the most difficult period for interpreting CCBF results. However, from then on especially after the first month, CCBF could reflect the graft’s actual vascular capacity and reserve. (..)  CCBF defined better than level of serum creatinine the graft function status at medium-term’’.

https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-018-1158-0

Two groups; 1. Patients who underwent kidney transplantation and had a short-term postoperative period follow-up (). This group was divided based on the need for dialysis (early graft function early graft function [EGF] and delayed graft function [DGF]). N = 29

2. Patients who underwent kidney transplantation and had a long-term postoperative period follow –up as outpatient (≥ 90 days).
This group was divided into creatinine tertiles. N = 37

All patients were on immunosuppression therapy and given steroids.

‘’ To build a time-intensity curve (TIC) using CEUS in non-immunological DGF (defined as the need for dialysis within 1 week) to understand the utility of CEUS in early transplantation.’’.

CEUS examination was performed using a convex transducer (Aplio 400) with Sonovue as the CA.

3 ROIs: segmental artery, medullary pyramid and subcapsular cortex.

An inbuilt TIC software was used to  derive a TIC and various perfusion parameters calculated including the time to peak (TTP) and the rise time (RT).

‘’It was not possible to differentiate EGF and DGF (excluding acute rejection) patients using TTP and RT derived from TIC analysis performed in three kidney territories (segmental artery, cortex and medulla). (..) These results seem to support that some approaches to increase renal blood flow in DGF are useless’’. This study points out that blood flow reduction may not be the cause of non-immunological DGF; therefore, CEUS would be useless in this case.

However, clear differences were found between the early and late groups. In fact, the largest difference was in between the whole early group and the lowest tertile of the late group (stable renal function). The RT and TTP differences pointed out that there may be blood shunting in renal dysfunction.

10.12659/pjr.883369

N = 16  (7F, 9M)

Mean age = 48.3 +/- 9.9

Each patient were on standard triple immunosuppressive therapy.

Evaluate and compare the size and echogenicity of perirenal haematomas in patients with kidney transplantation, which were assessed with both standard B examination followed by  CE-US.

Following standard B examination, suspected patient of having a perirenal haematoma underwent CE-US with Sonovue as the CA (2.4 mL/examination.

TIC curves were derived.

2 ROI: renal parenchyma and areas identified during standard US as haematomas.

‘’Dyanamic data loops allowed the acquision of identical kidney cross-sections and enabled measuring the echogenicity and thickness of the abnormalities at the same location.

The echogenicity was 6.2 x greater CE-US when compared to routine B examination. Furthermore, the size of the haematomas was larger in 62% of lesions detected with CE-US. In both cases, it was stastically significant.

CE-US allowed for a more detailed assessment of haematomas during the early-post operative period.

Patients who have undergone a percutaneous nephrolitomy and are on their first postioperative day.

N= 73 (81 examinations

Patients underwent both CEUS using Lumason (sulphur hexafluoride lipid type A)  and fluoroscopic anterograde nephrostogram in the first postoperative day.

Lumason was injected using an indwelling nephrostomy tube.

‘’Ureteral patency was confirmed by intravesical ultrasound (US) contrast.’’

Fluoroscopy was the reference standard

‘’Sensitivity and specificity were 96% and 57%, respectively. (..) the  relatively low specificity may have resulted from false negative results in fluoroscopy’’.

The hospital costs, resource use, portability, lack of ionizing radiation were all advantages of CEUS compared to fluoroscopy.

The only disadvantage noted compared to fluoroscopy was the lower levels of comfort noted by some patients.

10.1159/000346561

Patients who have undergone radical retropubic prostatectomy (RRP)

n=80

Investigate the diagnostic accuracy of transrectal CEUS and transrectal ultrasound (TRUS) to detect vesicourthral extravasation after RRP and to assess the strength of the vesicourethral anastomosis (VUA).

Use  conventional cystography (CG) as a reference .

CG, TRUS and CEUS were performed sequentially, but the examiner was blinded to the result of the previous tests.

CEUS was performed by emptying and   then refilling the bladder with NaCl and Sonovue (1:10)  as the CA.

‘’No stastically significant difference in detection of vesicourethral extravasation was found amount the three tests (p=0.472)’’.

‘’TRUS amd CEUS are able to provide information on the integrity of the VUA that is comparable with that of CG.’’