Trial Outcomes & Findings for Contrast-Enhanced Ultrasound for Kidney Cancer Subtyping and Staging (NCT NCT04021238)

NCT ID: NCT04021238

Last Updated: 2023-11-13

Results Overview

A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash\_In\_Slope parameter was generated. This metric indicates the change in contrast with time in the mass using bolus imaging. Bolus imaging injects a small amount of contrast agent and monitors the contrast agent as it flows in (wash-in) and out (wash-out) of the body/mass. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White.The Wash\_In\_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of curve.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 25 participants
• Primary outcome timeframe: Baseline- up to 3 minutes
• Results posted on: 2023-11-13

Participant Flow

Between 10/7/2020- 7/22/2022, 25 subjects consented and enrolled in the study at one center in North Carolina.

A total of 25 subjects were found eligible and consented to the study. One subject was withdrawn after enrollment and did not complete study imaging and 24 subjects enrolled in the study and underwent research imaging.

Participant milestones

Measure	Perflutren Lipid Microsphere Subjects with suspected kidney cancer and planned surgery were imaged using Definity® containing perflutren lipid microsphere contrast-enhanced ultrasound (US). Baseline B-mode US was performed to confirm the lesions being imaged.
Overall Study STARTED	24
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Contrast-Enhanced Ultrasound for Kidney Cancer Subtyping and Staging

Baseline characteristics by cohort

Measure	Perflutren Lipid Microsphere or Lumason n=24 Participants Subjects with suspected kidney cancer and planned surgery were imaged using Definity® containing perflutren lipid microsphere contrast-enhanced ultrasound (US). Baseline B-mode US was performed to confirm the lesions being imaged.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash_In_Slope parameter was generated. This metric indicates the change in contrast with time in the mass using bolus imaging. Bolus imaging injects a small amount of contrast agent and monitors the contrast agent as it flows in (wash-in) and out (wash-out) of the body/mass. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White.The Wash_In_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of curve.

Outcome measures

Measure	CEUS Imaging Parameters n=14 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma papillary carcinoma type	Clear Cell Papillary Clear cell papillary type	Chromophobe chromophobe type	Other other type
3D CEUS Generated Metrics in Kidney Mass: Wash_In_Slope	7.60 AU/second Interval 3.13 to 12.28	—	—	—	—

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash_In_intercept parameter was generated. This metric indicates the intensity level prior to infusion of contrast. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=white. This value was calculated using an equation for a line which has a slope and the intercept. The values were negative because they were calculated (not measured).

Outcome measures

Measure	CEUS Imaging Parameters n=14 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma papillary carcinoma type	Clear Cell Papillary Clear cell papillary type	Chromophobe chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass: Wash_In_intercept	-18.30 Units on a scale Interval -149.6 to 62.11	—	—	—	—

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash_Out_Slope parameter was generated. This metric indicates the change in contrast with time in the mass using bolus imaging. Bolus imaging injects a small amount of contrast agent and monitors the contrast agent as it flows in (wash-in) and out (wash-out) of the body/mass. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) value range was between 0=black and 255=White. The wash Out slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation.

Outcome measures

Measure	CEUS Imaging Parameters n=14 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma papillary carcinoma type	Clear Cell Papillary Clear cell papillary type	Chromophobe chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass: Wash_Out_Slope	-0.93 AU/second Interval -2.09 to -0.41	—	—	—	—

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash_Out_Intercept parameter was generated. This metric indicates the intensity level of contrast at a steady state of enhancement in the mass. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. This value was calculated using an equation for a line that has a slope and an intercept.

Outcome measures

Measure	CEUS Imaging Parameters n=14 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma papillary carcinoma type	Clear Cell Papillary Clear cell papillary type	Chromophobe chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass: Wash_Out_Intercept	125.84 units on a scale Interval 43.28 to 199.71	—	—	—	—

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) FR_a parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=white. The intensity was plotted by time. FR_a parameters were devised from an exponential fit. The exponential fit of the data provides the height of the curve.

Outcome measures

Measure	CEUS Imaging Parameters n=14 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma papillary carcinoma type	Clear Cell Papillary Clear cell papillary type	Chromophobe chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass: FR_a	102.84 Units on a scale Interval 61.01 to 152.8	—	—	—	—

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) FR_beta parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, 255=White. The intensity was plotted by time. FR_beta parameters were devised from an exponential fit. Exponential fit of the data provides the slope of the curve.

Outcome measures

Measure	CEUS Imaging Parameters n=14 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma papillary carcinoma type	Clear Cell Papillary Clear cell papillary type	Chromophobe chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass: FR_beta	0.16 AU/second Interval 0.03 to 0.77	—	—	—	—

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) volume parameter was generated. The volumes were generated using the ellipsoid equation on the CEUS image of the kidney mass.

Outcome measures

Measure	CEUS Imaging Parameters n=14 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma papillary carcinoma type	Clear Cell Papillary Clear cell papillary type	Chromophobe chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass: Volume	60.80 milliliters Interval 3.08 to 271.97	—	—	—	—

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash_In_Slope parameter was studied. This metric indicates the change in contrast intensity with time in the mass using bolus imaging. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The Wash_In_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of the curve.

Outcome measures

Measure	CEUS Imaging Parameters n=10 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=1 Participants papillary carcinoma type	Clear Cell Papillary n=1 Participants Clear cell papillary type	Chromophobe n=1 Participants chromophobe type	Other n=1 Participants other type
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_In_Slope	7.61 AU/second Standard Deviation 2.33	3.13 AU/second Standard Deviation NA Only 1 subject	4.23 AU/second Standard Deviation NA Only 1 subject	10.56 AU/second Standard Deviation NA Only 1 subject	12.28 AU/second Standard Deviation NA Only 1 subject

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash_In_intercept parameter was studied. This metric indicates the intensity level prior to infusion of contrast. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line which has a slope and the intercept. The values were negative because they were calculated (not measured).

Outcome measures

Measure	CEUS Imaging Parameters n=10 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=1 Participants papillary carcinoma type	Clear Cell Papillary n=1 Participants Clear cell papillary type	Chromophobe n=1 Participants chromophobe type	Other n=1 Participants other type
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_In_intercept	-11.02 Units on a scale Standard Error 58.96	-1.07 Units on a scale Standard Error NA Only 1 subject	31.12 Units on a scale Standard Error NA Only 1 subject	-53.10 Units on a scale Standard Error NA Only 1 subject	-122.88 Units on a scale Standard Error NA Only 1 subject

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash_Out_Slope parameter was studied. This metric indicates the change in contrast intensity with time in the mass using bolus imaging. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. Decreasing brightness is related to the slope of the curve. The Wash Out slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation.

Outcome measures

Measure	CEUS Imaging Parameters n=10 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=1 Participants papillary carcinoma type	Clear Cell Papillary n=1 Participants Clear cell papillary type	Chromophobe n=1 Participants chromophobe type	Other n=1 Participants other type
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_Out_Slope	7.62 AU/second Standard Deviation 2.33	3.13 AU/second Standard Deviation NA Only 1 subject	4.23 AU/second Standard Deviation NA Only 1 subject	10.56 AU/second Standard Deviation NA Only 1 subject	12.3 AU/second Standard Deviation NA Only 1 subject

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash_Out_Intercept parameter was studied. This metric indicates the intensity level of contrast at steady state of enhancement in the mass. The contrast-enhanced ultrasonogram (CEUS) Wash_Out_Intercept parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line which has a slope and the intercept.

Outcome measures

Measure	CEUS Imaging Parameters n=10 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=1 Participants papillary carcinoma type	Clear Cell Papillary n=1 Participants Clear cell papillary type	Chromophobe n=1 Participants chromophobe type	Other n=1 Participants other type
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_Out_Intercept	137.95 Units on a scale Standard Error 36.88	-0.43 Units on a scale Standard Error NA only 1 subject	118.53 Units on a scale Standard Error NA only 1 subject	139.01 Units on a scale Standard Error NA only 1 subject	148.49 Units on a scale Standard Error NA only 1 subject

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated FR_a parameter was studied. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR_a parameters were devised from an exponential fit. The exponential fit of the data provides the height of the curve.

Outcome measures

Measure	CEUS Imaging Parameters n=10 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=1 Participants papillary carcinoma type	Clear Cell Papillary n=1 Participants Clear cell papillary type	Chromophobe n=1 Participants chromophobe type	Other n=1 Participants other type
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. FR_a	105.34 Units on a scale Standard Error 27.09	0 Units on a scale Standard Error NA only 1 subject	0 Units on a scale Standard Error NA only 1 subject	0 Units on a scale Standard Error NA only 1 subject	0 Units on a scale Standard Error NA only 1 subject

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated FR_ beta parameter was studied. The contrast-enhanced ultrasonogram (CEUS) FR_beta parameter was generated. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR_beta parameters were devised from an exponential fit. The exponential fit of the data provides the slope of the curve.

Outcome measures

Measure	CEUS Imaging Parameters n=10 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=1 Participants papillary carcinoma type	Clear Cell Papillary n=1 Participants Clear cell papillary type	Chromophobe n=1 Participants chromophobe type	Other n=1 Participants other type
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. FR_beta	0.10 AU/second Standard Error 0.06	0 AU/second Standard Error NA only 1 subject	0 AU/second Standard Error NA only 1 subject	0 AU/second Standard Error NA only 1 subject	0 AU/second Standard Error NA only 1 subject

PRIMARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated volume parameter was studied. The volumes were generated using the ellipsoid equation on the CEUS image of the kidney mass.

Outcome measures

Measure	CEUS Imaging Parameters n=10 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=1 Participants papillary carcinoma type	Clear Cell Papillary n=1 Participants Clear cell papillary type	Chromophobe n=1 Participants chromophobe type	Other n=1 Participants other type
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Volume	57.93 milliliters Standard Deviation 81.07	260.78 milliliters Standard Deviation NA only 1 subject	3.08 milliliters Standard Deviation NA only 1 subject	4.77 milliliters Standard Deviation NA only 1 subject	3.16 milliliters Standard Deviation NA only 1 subject

SECONDARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black and 255=White. The Wash_In_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of the curve. The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated Wash_In_Slope parameter was studied.

Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to American Joint Cancer Committee. All masses in this study were in stage 0, I, II or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.

Outcome measures

Measure	CEUS Imaging Parameters n=1 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=8 Participants papillary carcinoma type	Clear Cell Papillary n=3 Participants Clear cell papillary type	Chromophobe n=2 Participants chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_In_Slope	12.27 AU/second Interval 12.27 to 12.27	6.91 AU/second Interval 3.51 to 10.57	6.72 AU/second Interval 3.26 to 9.51	9.32 AU/second Interval 2.55 to 11.13	—

SECONDARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor stage and CEUS-generated Wash_In_intercept parameter was studied. These values were generated by fitting the data to a linear equation. This metric indicates the intensity level prior to infusion of contrast. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line that has a slope and an intercept. The values were negative because they were calculated (not measured).

Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.

Outcome measures

Measure	CEUS Imaging Parameters n=1 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=8 Participants papillary carcinoma type	Clear Cell Papillary n=3 Participants Clear cell papillary type	Chromophobe n=2 Participants chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_In_intercept	-122.88 Units on a scale Interval -122.88 to -122.88	-9.36 Units on a scale Interval -149.6 to 62.0	-25.16 Units on a scale Interval -69.85 to -1.07	8.55 Units on a scale Interval -1.31 to 18.41	—

SECONDARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated Wash_Out_Slope parameter was studied. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The Wash_Out_Slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the AJCC. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm, Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.

Outcome measures

Measure	CEUS Imaging Parameters n=1 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=8 Participants papillary carcinoma type	Clear Cell Papillary n=3 Participants Clear cell papillary type	Chromophobe n=2 Participants chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_Out_Slope	-0.90 AU/second Interval -0.9 to -0.9	-1.1 AU/second Interval -2.09 to -0.41	-0.51 AU/second Interval -0.59 to -0.42	-0.86 AU/second Interval -0.95 to 0.79	—

SECONDARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated Wash_Out_Intercept parameter was studied. This metric indicates the intensity level of contrast at a steady state of enhancement in the mass. The contrast-enhanced ultrasonogram (CEUS) Wash_Out_Intercept parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line that has a slope and the intercept.

Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.

Outcome measures

Measure	CEUS Imaging Parameters n=1 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=8 Participants papillary carcinoma type	Clear Cell Papillary n=3 Participants Clear cell papillary type	Chromophobe n=2 Participants chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_Out_Intercept	148.49 Units on a scale Interval 148.49 to 148.49	139.36 Units on a scale Interval 90.17 to 199.71	85.72 Units on a scale Interval 43.2 to 122.56	154.1 Units on a scale Interval 131.05 to 177.15	—

SECONDARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated FR_a parameter was studied. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR_a parameters were devised from an exponential fit. The exponential fit of the data provides the height of the curve.

Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.

Outcome measures

Measure	CEUS Imaging Parameters n=1 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=8 Participants papillary carcinoma type	Clear Cell Papillary n=3 Participants Clear cell papillary type	Chromophobe n=2 Participants chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. FR_a	114.7 Units on a scale Interval 114.7 to 114.7	102.8 Units on a scale Interval 61.01 to 152.8	86.51 Units on a scale Interval 77.46 to 95.55	115.9 Units on a scale Interval 100.0 to 131.8	—

SECONDARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated FR_ beta parameter was studied. The contrast-enhanced ultrasonogram (CEUS) FR_beta parameter was generated. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR_beta parameters were devised from an exponential fit. The exponential fit of the data provides the slope of the curve.

Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.

Outcome measures

Measure	CEUS Imaging Parameters n=1 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=8 Participants papillary carcinoma type	Clear Cell Papillary n=3 Participants Clear cell papillary type	Chromophobe n=2 Participants chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. FR_beta	0.11 AU/second Interval 0.11 to 0.11	0.20 AU/second Interval 0.03 to 0.77	0.13 AU/second Interval 0.08 to 0.19	0.06 AU/second Interval 0.03 to 0.09	—

SECONDARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated volume was studied. The contrast-enhanced ultrasonogram (CEUS) volume was generated.

Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.

Outcome measures

Measure	CEUS Imaging Parameters n=1 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=8 Participants papillary carcinoma type	Clear Cell Papillary n=3 Participants Clear cell papillary type	Chromophobe n=2 Participants chromophobe type	Other other type
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Volume	3.16 milliliters Interval 3.16 to 3.16	15.42 milliliters Interval 3.07 to 40.7	194.43 milliliters Interval 50.53 to 271.97	70.64 milliliters Interval 30.38 to 110.91	—

SECONDARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between pooled tumor stage (tumor stages 0,1,2 versus tumor stage 3) and CEUS-generated Wash_In_Slope parameter was studied. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal values range between 0=black and 255=White. The Wash_In_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of the curve. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.

Outcome measures

Measure	CEUS Imaging Parameters n=12 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=2 Participants papillary carcinoma type	Clear Cell Papillary Clear cell papillary type	Chromophobe chromophobe type	Other other type
Pooled Kidney Mass Stage vs. 3D CEUS-generated Wash in Metrics	7.31 AU/second Standard Error 0.86	9.32 AU/second Standard Error 1.80	—	—	—

SECONDARY outcome

Timeframe: Baseline- up to 3 minutes

Population: Subjects who complete 3-D CEUS imaging and imaging qualities enough for CEUS parameters calculation.

The association between pooled tumor stage (tumor stages 0,1,2 versus tumor stage 3) and CEUS-generated Wash_Out_Slope parameter was studied. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The Wash_Out_Slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the AJCC. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found, Stage I = tumor size ≤7 cm, Stage II = tumor size >7 cm, Stage III includes tumors growing into a major vein or tissue, with no spread to lymph nodes.

Outcome measures

Measure	CEUS Imaging Parameters n=12 Participants CEUS-generated parameters : Wash\_In\_Slope generated from MATLAB for the analysis.	Papillary Carcinoma n=2 Participants papillary carcinoma type	Clear Cell Papillary Clear cell papillary type	Chromophobe chromophobe type	Other other type
Pooled Kidney Mass Stage Using 3D CEUS-generated Wash Out Metrics	-0.94 AU/second Standard Deviation 0.16	-0.87 AU/second Standard Deviation 0.08	—	—	—

Adverse Events

Perflutren Lipid Microsphere or Lumason

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Director, Clinical Research, Department of Radiology

UNC Chapel Hill

Phone: 919-966-4997

Email: rad_research@med.unc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place