An Investigation of Lesion Detection Accuracy for Artificial Intelligence–Based Denoising of Low-Dose 64Cu-DOTATATE PET Imaging in Patients with Neuroendocrine Neoplasms

Mathias Loft; Claes N. Ladefoged; Camilla B. Johnbeck; Esben A. Carlsen; Peter Oturai; Seppo W. Langer; Ulrich Knigge; Flemming L. Andersen; Andreas Kjaer

doi:10.2967/jnumed.122.264826

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FIGURE 1.
Joint histogram of PET intensity values for PET_25% (top) and PET_AI (bottom) versus reference PET_100%. Green line is identity line, and R² is shown above each image. Analysis was performed on training sets (n = 38).
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FIGURE 2.
Image similarity metrics: PSNR (top), MSE (middle), and SSIM (bottom). Error bars mark 95% CI. Analysis was performed on training sets (n = 38).
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FIGURE 3.
Distribution of Likert scale–defined image quality scores—3, moderate; 4, good; and 5, excellent (Likert scale–defined image quality scores 4 and 5 are considered diagnostic image quality)—on PET_100% and PET_AI. No patient had Likert scale–defined image quality score below 3. Analysis was performed on patient subset for clinical image analysis consisting of patients with ≤20 lesions per organ (n = 33).
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FIGURE 4.
Examples of full-dose PET_100%, low-dose PET_25%, and denoised PET_AI.
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FIGURE 5.
Patient with FN liver lesion. Patient had additional concordant TP liver lesions. Arrows mark lesion location on PET_100% and PET_100%/CT PET_25% shown for reference.
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FIGURE 6.
Patient with FP liver lesion on PET_AI. Patient had no lesions detected on PET_100%. Arrows mark lesion location on PET_AI and PET_AI/CT PET_25% shown for reference.
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FIGURE 7.
Distribution of TP, FP, and FN on PET_AI corresponding to number of lesions detected on PET_100%. Analysis was performed on patient subset for clinical image analysis consisting of patients with ≤20 lesions per organ (n = 33).

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TABLE 1.

Patient Characteristics

Characteristic	Data (n = 38)	Subset for clinical image analysis (n = 33)^*
Sex
Female	21 (55)	19 (58)
Male	17 (45)	14 (42)
Age (y)
Median	64	64
Range	37–84	37–84
Site of primary tumor
Small intestine	21 (55)	16 (49)
Pancreas	11 (29)	11 (33)
Lung	3 (8)	3 (9)
Other	3 (8)	3 (9)
Previous treatment^†
Surgery	29 (76)	27 (82)
Somatostatin analogs	23 (61)	18 (55)
Peptide receptor radionuclide therapy	12 (32)	8 (24)
Chemotherapy	10 (26)	7 (21)
Radiofrequency ablation (liver metastases)	2 (5)	2 (6)
Ki-67 proliferation index
<3%	9 (24)	8 (24)
3%–20%	26 (68)	22 (67)
>20%	3 (8)	3 (9)
Dose (MBq)^‡
PET_100%	191 (169–209)	191 (172–209)
PET_25%/PET_AI	48 (42–52)	48 (43–52)

↵* Patients with >20 lesions per organ (n = 5) were excluded for clinical image analysis. Patients used for clinical image analysis (n = 33) thus represent subset of all 38 patients included in training sets.
↵† Some patients received multiple treatments. Therefore, total number of treatments exceeds number of patients.
↵‡ Dose at PET_100% is ⁶⁴Cu-DOTATATE activity dose given to patient for PET/CT. PET_25% and PET_AI dose is derived from simulated equivalent dose at 25% of PET_100% dose.
Data are number followed by percentage in parentheses, except for age and dose (median and range).

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TABLE 2.

Number of Lesions Grouped by Organs and Regions in 33 Patients with NENs

Organ or region	No. of lesions PET_100%	No. lesions PET_AI	TP	FP	FN	Sensitivity^*	FDR^*
Liver	36	38	17	21	19	47 (30–65)	55 (38–71)
Pancreas	6	7	6	1	0	100 (54–100)	14 (0–58)
Abdominal	49	47	36	11	13	73 (59–85)	23 (12–38)
Extraabdominal LNs	5	6	5	1	0	100 (48–100)	17 (0–64)
Bone	17	12	10	2	7	59 (33–82)	17 (2–48)
Other	5	5	4	1	1	80 (28–99)	20 (1–72)
Overall	118	115	78	37	40	66 (57–75)	32 (24–42)

↵* Data for sensitivity and FDR are percentages followed by 95% CI in parentheses.
Abdominal = intestines, intraabdominal carcinosis, and intraabdominal lymph nodes (LNs); other = brain (1), ovary (1), thyroid or parathyroid (1), and skin (2). Analysis is performed on patient subset for clinical image analysis consisting of patients with ≤20 lesions per organ (n = 33).

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TABLE 3.

Certainty of Detected Lesions in 33 Patients with NENs

Organ or region	All lesions			TP			P^*	FN			FP
Organ or region	Total	C₁	C₀	Total	C₁	C₀	P^*	Total	C₁	C₀	Total	C₁	C₀
Liver
PET_100%	36	31	5	17	17	0	1.0	19	14	5	N/A	N/A	N/A
PET_AI	38	29	9	17	17	0		N/A	N/A	N/A	21	12	9
Pancreas
PET_100%	6	6	0	6	6	0	1.0	0	0	0	N/A	N/A	N/A
PET_AI	7	7	0	6	6	0		N/A	N/A	N/A	1	1	0
Abdominal
PET_100%	49	45	4	36	35	1	1.0	13	10	3	N/A	N/A	N/A
PET_AI	47	43	4	36	36	0		N/A	N/A	N/A	11	7	4
Extraabdominal LNs
PET_100%	5	5	0	5	5	0	1.0	0	0	0	N/A	N/A	N/A
PET_AI	6	5	1	5	5	0		N/A	N/A	N/A	1	0	1
Bone
PET_100%	17	16	1	10	10	0	1.0	7	6	1	N/A	N/A	N/A
PET_AI	12	11	1	10	9	1		N/A	N/A	N/A	2	2	0
Other
PET_100%	5	5	0	4	4	0	1.0	1	1	0
PET_AI	5	5	0	4	4	0		N/A	N/A	N/A	1	1	0
Overall
PET_100%	118	108	10	78	77	1	0.5	40	31	9	N/A	N/A	N/A
PET_AI	115	100	15	78	77	1		N/A	N/A	N/A	37	23	14

↵* P values calculated using McNemar test for paired proportions of distribution of C₁ and C₀ lesion scores in TP lesions on PET_100% vs. PET_AI.
Abdominal = intestines, intraabdominal carcinosis, and intraabdominal lymph nodes (LNs); N/A = not applicable; other = brain (1), ovary (1), thyroid or parathyroid (1), and skin (2); — = ▪▪▪. Analysis is performed on patient subset for clinical image analysis consisting of patients with ≤20 lesions per organ (n = 33).

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TABLE 4.

Characteristics of 33 Patients with NENs Based on Lesion Type

Parameter	TP-only or no lesions (n = 11)	FN (n = 16)	P^*	FP (n = 15)	P^*
Injected dose (MBq)	188 (181.5–201.5)	190.5 (184–198.9)	0.94	192.0 (184.0–195.6)	0.94
Weight (kg)	76.0 (67–81.5)	73.0 (64.3)	0.87	86.7 (74.0–97.5)	0.09
Dose/weight (MBq/kg)	2.5 (2.4–2.9)	2.6 (2.0–3.1)	0.82	2.3 (2.0–2.6)	0.07
Liver SUV_mean	5.0 (4.7–6.6)	5.0 (4.7–6.1)	0.79	6.1 (5.0–6.9)	0.22

↵* Mann–Whitney U test for comparison with reference (TP-only or no lesions group).
Data are shown as medians with interquartile range in parentheses. Analysis is performed on patient subset for clinical image analysis consisting of patients with ≤20 lesions per organ (n = 33). n refers to number of patients in each group. Patients may appear in both FN and FP groups if they have both FP and FN lesions. Accordingly, total number of patients exceeds 33.