Quantitative Differences Between the First and Second Injection of Contrast Agent in Contrast-Enhanced Ultrasonography of Feline Kidneys and Spleen.

Contrast-enhanced ultrasound is a valuable and safe technique for the evaluation of organ perfusion. Repeated injections of ultrasound contrast agent are often administered during the same imaging session. However, it remains unclear if quantitative differences are present between the consecutive microbubble injections. Therefore, the first and second injection of contrast agent for the left renal cortex, renal medulla and the splenic parenchyma in healthy cats were compared. A lower peak intensity and area under the curve were observed for the first injection of contrast agent in the feline kidney, both for the renal cortex and medulla, and spleen. Moreover, for the renal cortex, the time-intensity curve was steeper after the second injection. Findings from the present study demonstrate that a second injection of contrast agent provides stronger enhancement. The exact mechanism behind our findings remains unclear; however, saturation of the lung macrophages is believed to play an important role.

Theranostic mRNA-loaded microbubbles in the lymphatics of dogs: implications for drug delivery.

Microbubbles have shown potential as intralymphatic ultrasound contrast agents while nanoparticle-loaded microbubbles are increasingly investigated for ultrasound-triggered drug and gene delivery. To explore whether mRNA-nanoparticle loaded microbubbles could serve as theranostics for detection of and mRNA transfer to the lymph nodes, we investigate the behavior of unloaded and mRNA-loaded microbubbles using contrast-enhanced ultrasound imaging after subcutaneous injection in dogs. Our results indicate that both types of microbubbles are equally capable of rapidly entering the lymph vessels and nodes upon injection, and novel, valuable and detailed information on the lymphatic structure in the animals could be obtained. Furthermore, additional observations were made regarding the dynamics of microbubble lymph node uptake. Importantly, neither the microbubble migration distance within the lymphatics, nor the observed contrast signal intensity was influenced by mRNA-loading. Although further optimization of acoustic parameters will be needed, this could represent a first step towards ultrasound-guided, ultrasound-triggered intranodal mRNA delivery using these theranostic microbubbles.

The effect of anesthesia with propofol and sedation with butorphanol on quantitative contrast-enhanced ultrasonography of the healthy feline kidney.

Contrast-enhanced ultrasonography of the left kidney was performed using a commercial contrast agent in six healthy adult purpose-bred cats. A cross-over design was used to compare three protocols: (1) awake, (2) butorphanol (0.4 mg/kg IM), and (3) propofol (3.5-7.7 mg/kg IV boluses to effect). Time-intensity curves were created from two regions-of-interest drawn in the renal cortex. The curves were analyzed for blood flow parameters representing blood volume (base intensity, peak intensity, area-under-curve) and blood velocity (arrival time, time-to-peak, wash-in/out). There was no difference in the subjective enhancement pattern between the three protocols. No significant effect of butorphanol was observed in any of the perfusion parameters (P > 0.05). Propofol did not influence the most important perfusion parameter, area-under-the-curve, and is adequate for use in contrast-enhanced ultrasound studies.

Use of quantitative contrast-enhanced ultrasonography to detect diffuse renal changes in Beagles with iatrogenic hypercortisolism.

OBJECTIVE: To determine the feasibility of quantitative contrast-enhanced ultrasonography (CEUS) for detection of changes in renal blood flow in dogs before and after hydrocortisone administration. ANIMALS: 11 Beagles. PROCEDURE: Dogs were randomly assigned to 2 treatment groups: oral administration of hydrocortisone (9.6 mg/kg; n = 6) or a placebo (5; control group) twice a day for 4 months, after which the dose was tapered until treatment cessation at 6 months. Before treatment began and at 1, 4, and 6 months after, CEUS of the left kidney was performed by IV injection of ultrasonography microbubbles. Images were digitized, and time-intensity curves were generated from regions of interest in the renal cortex and medulla. Changes in blood flow were determined as measured via contrast agent (baseline [background] intensity, peak intensity, area under the curve, arrival time of contrast agent, time-to-peak intensity, and speed of contrast agent transport). RESULTS: Significant increases in peak intensity, compared with that in control dogs, were observed in the renal cortex and medulla of hydrocortisone-treated dogs 1 and 4 months after treatment began. Baseline intensity changed similarly. A significant increase from control values was also apparent in area under the curve for the renal cortex 4 months after hydrocortisone treatment began and in the renal medulla 1 and 4 months after treatment began. A significant time effect with typical time course was observed, corresponding with the period during which hydrocortisone was administered. No difference was evident in the other variables between treated and control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Quantitative CEUS allowed detection of differences in certain markers of renal blood flow between dogs treated orally with and without hydrocortisone. Additional studies are needed to investigate the usefulness of quantitative CEUS in the diagnosis of diffuse renal lesions.

Ultrasonography of the feline kidney: Technique, anatomy and changes associated with disease.

PRACTICAL RELEVANCE: Ultrasonography is an important tool for the detection of kidney disorders, which are among the most common health problems suffered by cats. It is more accurate than radiography for this purpose and is considered to be the reference modality for imaging the feline kidney, providing excellent visualisation of renal size, shape and internal architecture. Compared with more advanced imaging modalities, such as computed tomography or magnetic resonance imaging, ultrasonography is more accessible, less expensive, does not require general anaesthesia and allows real-time procedures to be performed. CLINICAL CHALLENGES: On ultrasound examination, focal or multifocal disorders may be readily identified, but diffuse changes are more challenging. B-mode ultrasonography is of limited use for differentiating between benign and malignant focal lesions. However, based on the presence and pattern of vascularity as an indicator of malignancy, contrast-enhanced ultrasonography allows distinction between benign and malignant focal renal lesions. AUDIENCE: This review provides a framework for the ultrasonographic approach to feline renal and perirenal disorders for the general practitioner. EVIDENCE BASE: Drawing on current literature relating to ultrasonographic examination of feline kidneys, the aim is to summarise ultrasonographic technique, anatomy and changes associated with renal and perirenal diseases.

Renal function and morphology in aged Beagle dogs before and after hydrocortisone administration.

Objectives of this study were to evaluate glomerular filtration rate (GFR), renal structural changes and proteinuria in aged Beagle dogs before and after hydrocortisone (HC) administration. Eleven Beagle dogs ≥10 years old were treated with either hydrocortisone (HC group, n = 6) or placebo (control group, n = 5). Urinary markers, GFR and kidney biopsies were evaluated before (T0), during (T16 wks) and after discontinuing HC administration (T24 wks). Results indicate that HC administration causes a significant increase in GFR. At all time points except T16 wks, proteinuria was higher in the control group than in the HC group, and there was no significant difference in urinary markers between groups. At T16 wks, proteinuria, urinary albumin-to-creatinine (c) ratio, immunoglobulin G/c and retinol-binding protein/c were higher compared to baseline in the HC group. At T0, rare to mild renal lesions were detected in all HC dogs and rare to moderate changes in all control dogs. Glomerulosclerosis progressed in both groups until T24 wks. Tubular atrophy was detected in three HC dogs at T16 wks and T24 wks, but also in five control dogs throughout the study. At every time point, five HC dogs and all control dogs had rare to moderate interstitial inflammation. Rare to mild interstitial fibrosis was found in up to three HC dogs at T16 wks and T24 wks, and severe fibrosis in one HC dog at T24 wks. Up to four control dogs had rare to mild fibrosis at all time points. These findings indicate that clinically healthy, aged Beagle dogs may have considerable renal lesions and proteinuria, which could have implications for experimental or toxicological studies. Additional research is needed to elucidate glucocorticoid effects on renal structure, but functional changes such as hyperfiltration and proteinuria warrant attention to kidney function of canine patients with Cushing's syndrome or receiving exogenous glucocorticoids.

Contrast harmonic ultrasound appearance of consecutive percutaneous renal biopsies in dogs.

Ultrasound-guided percutaneous renal biopsy may be associated with complications, especially when using larger needles. Contrast harmonic ultrasound increases blood pool echo intensity, enhancing parenchymal lesions. Therefore, contrast harmonic ultrasound is a potential alternative screening method for postbiopsy renal lesions. Renal biopsies were performed using 14 G needles in 11 healthy Beagles, at three occasions: 0 ("Baseline Biopsy"; BB), 4 ("Biopsy 2"; B2), and 6 months ("Biopsy 3"; B3). Ultrasound and contrast harmonic ultrasound of biopsied kidneys were performed approximately 30 min after biopsy (week 0) at BB and B2, and repeated once every week (weeks 1-3) until normal appearance. At B3, only contrast harmonic ultrasound was performed, both immediately and 30-min postbiopsy. Contrast harmonic ultrasound images were reviewed using subjective and semiquantitative methods to describe lesions including number, shape, size, sharpness, echogenicity, and evolution. More renal lesions were detected with contrast harmonic ultrasound (22/22) compared with conventional ultrasound (14/22). The majority appeared at week 0 as hypoechoic tract(s) (27/33), the other (6/ 33) as ill-defined areas or area/tract combination, all having variable size, shape, and echogenicity. Seven tracts had a small subcapsular hematoma. In most kidneys, similar or gradual decrease of size and sharpness, and increased echogenicity was observed until normal appearance occurred at week 1 (1/22), week 2 (18/22), or week 3 (22/22). Two Beagles developed complications. At B3, immediately postbiopsy, tracts were hyperechoic in 9/11 kidneys, becoming hypoechoic again 30 min later. Contrast harmonic ultrasound is a valuable method to evaluate postbiopsy renal lesions in dogs.

Contrast-enhanced ultrasonography of the normal canine adrenal gland.

Contrast-enhanced ultrasonography is useful in differentiating adrenal gland adenomas from nonadenomatous lesions in human patients. The purposes of this study were to evaluate the feasibility and to describe contrast-enhanced ultrasonography of the normal canine adrenal gland. Six healthy female Beagles were injected with an intravenous bolus of a lipid-shelled contrast agent (SonoVue(®) ). The aorta enhanced immediately followed by the renal artery and then the adrenal gland. Adrenal gland enhancement was uniform, centrifugal, and rapid from the medulla to the cortex. When maximum enhancement was reached, a gradual homogeneous decrease in echogenicity of the adrenal gland began and simultaneously enhancement of the phrenicoabdominal vessels was observed. While enhancement kept decreasing in the adrenal parenchyma, the renal vein, caudal vena cava, and phrenicoabdominal vein were characterized by persistent enhancement until the end of the study. A second contrast enhancement was observed, corresponding to the refilling time. Objective measurements were performed storing the images for off-line image analysis using Image J (ImageJ(©) ). The shape of the time-intensity curve reflecting adrenal perfusion was similar in all dogs. Ratios of the values of the cortex and the medulla to the values of the renal artery were characterized by significant differences from initial upslope to the peak allowing differentiation between the cortex and the medulla for both adrenal glands only in this time period. Contrast-enhanced ultrasonography of the adrenal glands is feasible in dogs and the optimal time for adrenal imaging is between 5 and 90 s after injection.

Contrast harmonic ultrasonographic appearance of focal space-occupying renal lesions.

To describe the contrast-enhanced ultrasonographic appearance of various focal, space-occupying renal lesions and determine its value in their detection and characterization. Following baseline B-mode sonography of 15 dogs and one cat with renal space-occupying lesion(s), contrast-enhanced sonography was performed. The resulting images were evaluated qualitatively using conspicuity and number of lesions, and enhancement patterns were assessed during early arterial and late corticomedullary phases. Renal lesions were malignant in the cat (renal cell carcinoma) and 10 dogs (four renal cell carcinoma, two histiocytic sarcoma, one B-cell lymphoma, two hemangiosarcoma metastasis, one ch emodectoma metastasis) and benign in five dogs (two abscesses, one traumatic hematoma, one idiopathic hematoma, one hemorrhagic/necrotic nodule). Substantial overlap was present regarding the baseline sonographic features of benign vs. malignant lesions. With contrast-enhanced sonography, all renal cell carcinomas were characterized by large tortuous arteries, sometimes enhancing slightly earlier than vessels in the surrounding normal kidney. During the late corticomedullary phase, renal cell carcinomas had intense homo- or heterogeneous, iso- or slightly hypoechoic enhancement, which decreased progressively. Compared with renal cell carcinoma, histiocytic sarcoma and lymphoma had smaller and less obvious arteries, and an earlier loss of enhancement during the late phase. All hemangiosarcoma metastases appeared as nonenhancing nodules during the early arterial and late corticomedullary phases of enhancement, and additional lesions were detected. Histiocytic sarcoma and benign lesions had increased conspicuity with baseline sonography. The descriptions provided herein will be valuable as more work is done to establish the role of contrast-enhanced sonography in the assessment of renal lesions.

B-mode and contrast-enhanced sonographic assessment of accessory spleen in the dog.

Four dogs with an accessory spleen are described. The accessory spleens appeared as a round-to-triangular structure located in the perisplenic area. They were homogeneous and isoechoic with the adjacent spleen. Contrast-enhanced ultrasound was performed using a second generation microbubble contrast medium (sulfur hexafluoride). The type and timing of enhancement of the accessory spleen was similar to that of the parent spleen. Contrast-enhanced ultrasound is a noninvasive modality useful in distinguishing an accessory spleen from a mass of another origin.

Review of clinical characteristics and applications of contrast-enhanced ultrasonography in dogs.

Contrast-enhanced ultrasonography improves detection of the perfusion and vascularity of organs. Its main indication is the assessment of focal lesions in the liver and spleen, particularly with regard to differentiating between benign and malignant processes. Evidence suggests that contrast-enhanced ultrasonography may be a valuable alternative to invasive diagnostic procedures such as fine-needle aspiration and core biopsy.