Individually optimized contrast-enhanced 4D-CT for radiotherapy simulation in pancreatic adenocarcinoma Wookjin Choi, Ming Xue, Barton Lane, Min Kyu Kang, Kruti Patel, William Regine, Paul Klahr, Jiahui Wang, Shifeng Chen, Warren D'Souza, Wei LuMedical Physics, Memorial Sloan Kettering Cancer CenterRadiation Oncology and Radiology, University of Maryland School of Medicine

Purpose

Results

Method

To develop an individually optimized contrast-enhanced (CE) 4D-CT for radiotherapy simulation in pancreatic ductal adenocarcinoma (PDA).

• Ten PDA patients were enrolled and underwent three CT scans

– Clinical standard: A 4D-CT immediately following a CE 3D-CT

– Proposed protocol: A single individually optimized CE 4D-CT using a test injection to estimate the peak contrast enhancement time and to optimize the delay time.

• Three physicians contoured the tumor and pancreatic tissues.

• Image quality scores, tumor volume, motion, image noise, tumor-to-pancreas contrast, and contrast-to-noise ratio (CNR) were compared in the three CTs.

• Inter-observer variations in contouring the tumor were as well as evaluated using simultaneous truth and performance level estimation (STAPLE).

• The CE 4D-CT was largely comparable to CE 3D-CT– Image quality, enhancement, and contrast• High potential for simultaneously delineating the

tumor and quantifying tumor motion with a single scan.

• Contrast enhancement in PDA is still poor, large inter-observer variations in contouring tumors.

• Image qualities of CE 3D-CT and CE 4D-CT were comparable, and both were significantly better than 4D-CT.

• Tumor-to-pancreas contrast in CE 3D-CT and CE 4D-CT were comparable, and the later was higher than 4D-CT.

• Noise in CE 3D-CT was much lower than 4D-CT and CE 4D-CT.

• CNR was not significantly different between CE 3D-CT and CE 4D-CT.

• Both GTV50% in CE 4D-CT and GTV in CE 3D-CT were significantly smaller than GTV50% in 4D-CT.

• Tumor motion were comparable.• Large inter-observer variations in all three CTs

CE 3D-CT CE 4D-CT4D-CTFig. 2. Three physicians visually scored image quality, and contoured the tumor (red, T) and pancreatic tissue (blue, P).

𝐶𝑁𝑅=𝐶𝜎 𝑓,T

P

•  

Conclusion

  CE 3D-CT 4D-CT CE 4D-CTPancreas (HU) 49.2 ± 12.3 44.6 ± 15.9* 75.5 ± 21.2*

Tumor (HU) 53.0 ± 9.2* 58.9 ± 14.3* 76.3 ±15.0*

Tumor-to-pancreas contrast (HU)

15.5 ± 20.7 9.2 ± 9.2* 16.7 ± 12.3

Noise (HU) 12.5 ± 3.9* 19.4 ± 5.8 22.1 ± 5.7*

CNR 1.4 ± 1.9* 0.6 ± 0.7* 0.8 ± 0.6

  CE 3D-CT 4D-CT CE 4D-CTGeneralImage

Quality

Anatomical details 4.1 ± 0.8 2.5 ± 0.6 3.6 ± 0.8Motion artifacts 3.9 ± 1.0 3.4 ± 0.9 3.7 ± 0.8Beam hardening 4.2 ± 0.8 3.3 ± 0.9 3.5 ± 0.8Enhancement 3.2 ± 1.0 1.7 ± 0.9 3.3 ± 1.0

Regional Vessel Definition 4.2 ± 1.1 2.7 ± 1.5 4.1 ± 1.3Overall Average 4.0 ± 0.5 2.6 ± 0.5 3.8 ± 0.4Signed rank test (P) <0.001*,

vs. 4D-CT<0.001*,

vs. CE 4D-CT0.082,

vs. CE 3D-CT

    4D-CT CE 4D-CT P

Volume (cm3)

GTV50% 42.0 ± 35.1 22.8 ± 18.9 0.005*

IGTV4 56.0 ± 38.1 32.8 ± 26.4 0.005*

GTV Motion(mm)

LR 2.3 ± 1.7 1.1 ± 0.5 0.14AP 2.8 ± 1.6 2.6 ± 1.6 0.80SI 6.0 ± 1.7 5.4 ± 1.6 0.393D 7.2 ± 2.0 6.2 ± 1.9 0.17

Table 1. Image Quality Scores

Table 2. Quantitative Analysis

Table 3. Tumor Volume and Motion

Fig. 5. Inter-observer variation in contouring tumors

Supported in part by Philips Healthcare, Inc. and NIH Grant No. R01CA172638

*Contact: Wei Lu, Ph.D., luw@mskcc.org

We can determine optimal delay time Tdelay

4D-CT Acquisition Contrast Injection

LO

4D-C

T Sc

an L

engt

h

Org

an

Tpeak

Tdelay = LO/V- Tpeak

Contrast Enhancement Curve

Time (s)

Enhancement (HU)

a

c

b

de

Time when the organ is scanned over (Lo/V)

Time when organ reaches peak enhancement Tpeak

Synchronize

Using a test injection enhancement curve {Xue et al., 2012. Med. Phy. 39: 3903-3903}.

ROI in aorta

{Bae 2010. Radiology 256: 32-61}

Enhancement (HU)

Time (Sec)

0 5 10 15 20 25 30 35 45

105

100

959085807570656055

Typical transit time

Injection duration

Typical arrival time

𝑇 𝑝𝑒𝑎𝑘=T ID+15 s+(T arr−20 s )

Tarr = 24.2 s

Tpeak

Pancreas

Scores ranged from 1 to 5, with 1 being “very poor” and 5 being “excellent.”, and *Significant at 0.05.

*Significant at 0.05.

*Significant at 0.05.

Fig.1. Regions adjacent to the tumor–pancreas boundary were selected to measure contrast.

Fig. 4. Determine the delay time.

Fig. 3. Estimate time to peak enhancement

78.0% 73.7%66.0%66.5%

72.7%

55.6%

72.2% 72.5%61.9%

0.0%10.0%20.0%30.0%40.0%50.0%60.0%70.0%80.0%90.0%

Sensitivity Specificity JaccardCE 3D-CT 4D-CT CE 4D-CT