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Original ResearchFree Access

Measuring Glucose Uptake in Primary Invasive Breast Cancer Using Simultaneous Time-of-Flight Breast PET/MRI: A Method Comparison Study with Prone PET/CT

Published Online:Jan 15 2021https://doi.org/10.1148/rycan.2021200091
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Abstract

Purpose

To compare the measurement of glucose uptake in primary invasive breast cancer using simultaneous, time-of-flight breast PET/MRI with prone time-of-flight PET/CT.

Materials and Methods

In this prospective study, women with biopsy-proven invasive breast cancer undergoing preoperative breast MRI from 2016 to 2018 were eligible. Participants who had fasted underwent prone PET/CT of the breasts approximately 60 minutes after injection of 370 MBq (10 mCi) fluorine 18 fluorodeoxyglucose (18F-FDG) followed by prone PET/MRI using standard clinical breast MRI sequences performed simultaneously with PET acquisition. Volumes of interest were drawn for tumors and contralateral normal breast fibroglandular tissue to calculate standardized uptake values (SUVs). Spearman correlation, Wilcoxon signed ranked test, Mann-Whitney test, and Bland-Altman analyses were performed.

Results

Twenty-three women (mean age, 50 years; range, 33–70 years) were included. Correlation between tumor uptake values measured with PET/MRI and PET/CT was strong (rs = 0.95–0.98). No difference existed between modalities for tumor maximum SUV (SUVmax) normalized to normal breast tissue SUVmean (normSUVmax) (P = .58). The least amount of measurement bias was observed with normSUVmax, +3.86% (95% limits of agreement: −28.92, +36.64).

Conclusion

These results demonstrate measurement agreement between PET/CT, the current reference standard for tumor glucose uptake quantification, and simultaneous time-of-flight breast 18F-FDG PET/MRI.

Keywords: Breast, Comparative Studies, PET/CT, PET/MR

Supplemental material is available for this article.

© RSNA, 2021

See also the commentary by Mankoff and Surti in this issue.

Summary

Measurement agreement of the glucose uptake in primary invasive breast cancer was demonstrated between PET/CT, the current reference standard, and simultaneous time-of-flight breast fluorine 18 fluorodeoxyglucose PET/MRI.

Key Points

  • ■ Correlation between fluorine 18 fluorodeoxyglucose tumor uptake values measured with breast PET/MRI and PET/CT was strong (rs = 0.95–0.98).

  • ■ No difference existed between breast PET/MRI and PET/CT for tumor maximum standardized uptake value (SUVmax) normalized to normal breast tissue SUVmean (normSUVmax; 6.3 ± 1.0 vs 6.3 ± 1.1, respectively; P = .58).

  • ■ The least amount of measurement bias between breast PET/MRI and PET/CT was observed with normSUVmax (+3.86%; 95% limits of agreement: −28.92, +36.64).

  • ■ Comparable results between 10-minute and 30-minute image acquisition times indicate that simultaneous breast PET/abbreviated MRI is also feasible.

Introduction

Breast cancer accounts for the majority of new cancers diagnosed and cancer deaths for women worldwide (1). Breast cancer was recently estimated to account for 24% (2 088 849 of 8 622 539) of new cancers diagnosed and 15% (626 679 of 4 169 387) of cancer deaths in women across 185 countries (1). In the United States, 30% (276 480 of 912 930) of new cancers diagnosed and 15% (42 170 of 285 360) of cancer deaths in women are estimated to be caused by breast cancer in 2020 (2).

Molecular imaging provides a noninvasive method for detecting and providing functional characterization of breast cancer. The most commonly used molecular imaging agent for oncology is fluorine 18 fluorodeoxyglucose (18F-FDG) that accumulates within tissues with high glucose metabolism. 18F-FDG PET/CT whole-body imaging can be used for identifying distant metastases in patients with newly diagnosed locally advanced and inflammatory breast cancer (3,4), for restaging patients with suspected recurrence (5), and for monitoring treatment response for patients with locally advanced and metastatic breast cancer (6,7).

Contrast-enhanced MRI of the breasts produces high-spatial-resolution images to anatomically characterize tumor morphology and functionally assess lesion perfusion, characterized by the time-dependent uptake and washout of gadolinium-based contrast agents (8,9). Breast MRI is the most sensitive method for breast cancer detection and is used clinically as a supplemental screening tool for women at increased lifetime risk of breast cancer development, preoperative staging for women with newly diagnosed breast cancer, and assessment of response to neoadjuvant therapy (10).

There is increasing interest in combining high-spatial-resolution anatomic and perfusion information obtained using MRI with functional metabolic information obtained from PET for a more comprehensive analysis of breast lesions. Historically, this has been performed by coregistration of images acquired separately from a dynamic contrast-enhanced breast MRI and a PET/CT performed in the prone position (11–15). With the advent of combined PET/MRI scanners, breast PET/MRI can now be performed in a single imaging session (16–20). Depending on the scanner design, the acquisition of PET and MRI data occurs either sequentially or simultaneously. Multichannel radiofrequency coils have been designed specifically for breast PET/MRI to limit attenuation, which is important for accurate quantification of radiopharmaceutical uptake (21–23).

The clinical utility of breast PET/MRI for diagnosis and local-regional staging of breast cancer has been studied using subjective, visual assessment of 18F-FDG uptake (19,24–26). Results from recent small studies suggest that multiparametric breast PET/MRI with 18F-FDG may have an advantage for predicting therapy response compared with either modality alone (27–30). Therapy response assessment is an established clinical application of PET/CT, and substantial efforts have been invested to standardize its use to measure quantitative imaging biomarkers for oncologic treatment response through national initiatives such as the Quantitative Imaging Biomarkers Alliance (31). Given the fundamentally different attenuation methods between PET/CT and PET/MRI (32), it is important to verify semiquantitative radiopharmaceutical uptake parameters between these two modalities if intended to be used to assess therapy response. Previous studies were performed with patients positioned supine without a dedicated breast radiofrequency coil using an avalanche photodiode-based PET/MRI scanner without time-of-flight capability, which are major quantitative limitations (33–38). A newer simultaneous PET/MRI scanner is now clinically available which uses silicon photomultipliers with time-of-flight capability, which offers increased PET sensitivity as well as the potential for dose reduction of 18F-FDG (18,39). The future success of breast PET/MRI implementation for therapy response assessment hinges on establishing its quantitative accuracy for measuring radiopharmaceutical uptake.

The overall goal of this research was to develop and test a simultaneous, time-of-flight PET/MRI acquisition protocol specific for breast imaging and quantitative evaluation of primary breast cancer. We hypothesized that semiquantitative assessment of tumor glycolytic activity using simultaneous breast PET/MRI would be feasible and comparable to that of prone PET/CT using harmonized PET reconstruction parameters. The purpose of this method comparison study was to compare tumor uptake of 18F-FDG measured with simultaneous, time-of-flight breast PET/MRI with uptake obtained with prone time-of-flight PET/CT in participants with newly diagnosed primary invasive breast cancer.

Materials and Methods

Study Design

This Health Insurance Portability and Accountability Act–compliant, institutional review board–approved (#2015–0563) single-institution, prospective study was performed from January 2016 to August 2018 via convenience sampling. Women 18 years of age or older with biopsy-proven invasive breast cancer undergoing preoperative breast MRI were eligible. There are no established guidelines for patient selection criteria for use of preoperative breast MRI; however, surgeons at our institution are more likely to order breast MRI for women younger than 50 years of age at diagnosis, with invasive lobular carcinoma, with mammographically dense breasts, and with mammographically occult breast cancer. Participants who were pregnant, lactating, had breast implants, underwent surgical excision or neoadjuvant therapy for the current breast cancer, had a body habitus that exceeded the bore of the PET/MRI scanner (body mass index greater than 36 kg/m2), or had contraindications to MRI were not eligible. Eligible participants identified through screening were approached for study enrollment. There were 44 eligible women contacted who declined participation. A total of 23 eligible women provided written informed consent and were included in the study. None of the eligible participants who consented to the study were excluded from analysis. Participant demographics, tumor histologic and pathologic subtype, and clinical information were obtained from the electronic medical record. As indicated by the fifth edition of the American College of Radiology Breast Imaging Reporting and Data System Atlas (40), scheduling preoperative breast MRI for patients with newly diagnosed breast cancer does not require menstrual cycle timing, and thus, menstrual cycle information was not obtained.

Imaging Protocol

The single-injection, dual-imaging protocol is illustrated in Figure 1. For all participants, the sequence of imaging was standardized with PET/CT performed first followed by PET/MRI. The Discovery PET/CT 710 (GE Healthcare) and Signa PET/MR (GE Healthcare) scanners were used for this study. The Discovery 710 system is composed of a PET component with lutetium-based scintillator crystals and conventional photomultiplier tubes with time-of-flight capability and a 64-section CT (41). The Signa PET/MRI system is composed of lutetium-based scintillator crystals and solid-state silicon photomultipliers with time-of-flight capability integrated within a wide-bore 3.0-T MRI scanner (18).

Single fluorine 18 fluorodeoxyglucose (18F-FDG) injection experimental design and dual hybrid imaging acquisition timeline.

Figure 1: Single fluorine 18 fluorodeoxyglucose (18F-FDG) injection experimental design and dual hybrid imaging acquisition timeline.

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After fasting for at least 6 hours, women underwent PET/CT of the breasts without intravenous contrast material 55 minutes ± 4.9 (standard deviation) (range, 46–66 minutes) after injection of an average of 381.1 MBq (range, 321.9–425.5 MBq; 10.3 mCi, range, 8.7–11.5 mCi) of 18F-FDG (SOFIE). Blood glucose levels were 90 mg/dL ± 10.4 (range, 75–109 mg/dL). Average body mass index was 28.8 kg/m2 (range, 21.9–35.8 kg/m2). Women were scanned prone at one bed position centered at the level of the breasts for 10 minutes using a modified breast MRI coil housing with metal components removed to replicate positioning between the PET/CT and PET/MRI scanners (Figure E1 [supplement]). A low-dose CT scan was obtained for attenuation correction using the following: 140 kVp, noise index of 25, 0.5-second rotation time, 0.516 pitch, 70-cm reconstructed field of view, matrix size of 512 × 512, and 5-mm section thickness with 3.27-mm section intervals. The average CT dose-length product was 182.4 mGy · cm ± 0.16 (range, 182.06–182.73 mGy · cm). Whole-body PET/CT coverage was not performed as part of this research study.

Women subsequently underwent breast PET/MRI using an eight-channel breast coil (GE Healthcare) 83 minutes ± 8 (range, 75–113 minutes) after injection of 18F-FDG. A standard prone clinical breast MRI examination was performed, including axial precontrast three-plane localizer, two-dimensional T2-weighted fat-suppressed fast spin-echo, and diffusion-weighted imaging. Axial T1-weighted fat-suppressed fast spoiled gradient-echo images prior to and three times after the administration of intravenous gadolinium-based contrast agent (gadobenate dimeglumine; 0.1 mmol/kg; MultiHance; Bracco Diagnostics) power injected at 2 mL/min were obtained. MRI sequences were performed simultaneously with PET data acquisition for 30 minutes. Precontrast Dixon-based fat and water images were obtained for MR attenuation correction using the following: 5° flip angle, echo times of 1.1 and 2.2 msec, repetition time of 4.0 msec, and a bandwidth of ±167 kHz. Data were acquired over a 50 × 50 × 33 cm3 field of view with a 256 × 128 × 64 matrix size. All MR attenuation correction data were reviewed by an experienced medical physicist (L.H.B., 6 years of experience) for quality and assessed for any artifacts.

PET emission data were corrected for randoms, dead time, scatter, and attenuation. PET images were reconstructed using settings that harmonized maximum standardized uptake values (SUVmax) across scanners using the American College of Radiology phantom. PET/CT reconstruction parameters included: three ordered-subset expectation maximization iterations, 24 subsets, 5.0-mm post filter, standard axial filter, time-of-flight, SharpIR, 70-cm field of view, and 192 × 192 matrix size. PET/MRI reconstruction parameters included: three ordered-subset expectation maximization iterations, 28 subsets, 6-mm post filter, standard axial filter, time-of-flight, SharpIR, 60-cm field of view, and 192 × 192 matrix size.

Image Assessment

For all women, the biopsy-proven malignancy contained a marker clip to confirm tumor location. For tumor SUV measurements, volumes of interest were drawn with an isocontour using a threshold of 30% of the lesion’s SUVmax (Mirada Medical XD3 v3.6). For normal breast tissue SUV, a 1-cm3 spherical volume of interest was applied in the normal fibroglandular tissue of the contralateral breast. A board-certified radiologist (A.M.F.) with 7 years of experience in breast imaging and molecular imaging performed the measurements on the images from the PET/CT and the 0–30-minute reconstructed PET/MRI. Volumes of interest were propagated automatically from the 0–30-minute reconstructed PET/MRI data set to the 0–10-minute reconstructed PET/MRI data set.

Statistical Analysis

A sample size of 23 was chosen a priori based on the expectation that the lower limit for a one-sided 95% CI for the Pearson correlation coefficient will exceed 0.80 when the correlation estimate is 0.90 (42). Sample size calculations were performed using PASS 13 (NCSS, Kaysville, Utah). Continuous measurements are represented as mean ± standard error. Corresponding median and range values are included in Table E1 (supplement) and Table E2 (supplement). Bland-Altman analysis was performed to determine measurement bias and 95% limits of agreement (LoA) (43,44). Comparisons between PET/MRI and PET/CT 18F-FDG uptake values were analyzed using Spearman rank correlation and Wilcoxon signed ranked test. The Mann-Whitney test was used to analyze the association of 18F-FDG uptake parameters with tumor characteristics including histologic subtype (invasive ductal carcinoma vs invasive lobular carcinoma), grade (1 and 2 vs 3), and estrogen receptor (ER) status (positive vs negative). P values less than .05 were considered significant. Statistical analyses were performed using Prism 6.04 (GraphPad Software, San Diego, Calif) and SPSS Statistics version 25 (IBM, Armonk, NY).

Results

Study Population Characteristics

Twenty-three women (mean age, 50 years; range, 33–70 years) with 24 separate biopsy-proven sites of invasive breast carcinoma participated in the study and all completed both the PET/CT and PET/MRI examinations, meeting the predesignated sample size. Pathologic findings included 16 invasive ductal carcinomas, six invasive lobular carcinomas, one invasive mammary carcinoma with lobular features, and one invasive mucinous carcinoma (Table 1). Most tumors were histologic grades 1 or 2 (18 of 24; 75%) and were ER positive, progesterone receptor positive, and human epidermal growth factor receptor 2 negative (19 of 24, 79%). The average lesion size was 3.8 cm (range, 1.1–8.8 cm) measured with MRI.

Table 1: Participant and Lesion Characteristics

Table 1:

Imaging Examination Quality

All examinations were performed once without the need for any technical repeat examinations. No substantial imaging artifacts were observed. Representative examples demonstrating the imaging examination quality and reproducibility in participant positioning between PET/CT and PET/MRI examinations are included in Figures 2 and 3. Visual 18F-FDG uptake was identified for all biopsy-proven malignant lesions, including a small (1.1-cm), grade 1, ER-positive, progesterone receptor−positive, and human epidermal growth factor receptor 2−negative invasive ductal carcinoma (Fig 3).

Fluorine 18 fluorodeoxyglucose (18F-FDG) breast PET/MRI and prone PET/CT images of high-grade invasive ductal carcinoma (IDC). Axial images from participant 9 (Table 1) who was a 59-year-old woman with grade 3 IDC (estrogen receptor–positive, progesterone receptor–positive, and human epidermal growth factor receptor 2–negative) measuring 2.9-cm in the right breast (arrow). The PET/MRI tumor maximum standardized uptake value (SUVmax) was 6.73, tumor mean standardized uptake value (SUVmean) was 4.11, and normal breast SUVmean was 0.88. The PET/CT tumor SUVmax was 6.11, tumor SUVmean was 3.04, and normal breast SUVmean was 0.70. The sequence shown for MRI is the early-phase postcontrast T1-weighted fat-suppressed fast spoiled gradient-echo images.

Figure 2: Fluorine 18 fluorodeoxyglucose (18F-FDG) breast PET/MRI and prone PET/CT images of high-grade invasive ductal carcinoma (IDC). Axial images from participant 9 (Table 1) who was a 59-year-old woman with grade 3 IDC (estrogen receptor–positive, progesterone receptor–positive, and human epidermal growth factor receptor 2–negative) measuring 2.9-cm in the right breast (arrow). The PET/MRI tumor maximum standardized uptake value (SUVmax) was 6.73, tumor mean standardized uptake value (SUVmean) was 4.11, and normal breast SUVmean was 0.88. The PET/CT tumor SUVmax was 6.11, tumor SUVmean was 3.04, and normal breast SUVmean was 0.70. The sequence shown for MRI is the early-phase postcontrast T1-weighted fat-suppressed fast spoiled gradient-echo images.

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Fluorine 18 fluorodeoxyglucose breast (18F-FDG) PET/MRI and prone PET/CT images of small, low-grade invasive ductal carcinoma. Axial images from participant 11 (Table 1) who was a 65-year-old woman with a grade 1 IDC (estrogen receptor–positive, progesterone receptor–positive, and human epidermal growth factor receptor 2–negative) measuring 1.1 cm in the right breast (arrow). PET/MRI tumor maximum standardized uptake value (SUVmax) was 2.25, tumor mean standardized uptake value (SUVmean) was 1.33, and normal breast SUVmean was 1.16. The PET/CT tumor SUVmax was 1.70, tumor SUVmean was 0.77, and normal breast SUVmean was 1.57. The sequence shown for MRI is the early-phase postcontrast T1-weighted fat-suppressed fast spoiled gradient-echo images.

Figure 3: Fluorine 18 fluorodeoxyglucose breast (18F-FDG) PET/MRI and prone PET/CT images of small, low-grade invasive ductal carcinoma. Axial images from participant 11 (Table 1) who was a 65-year-old woman with a grade 1 IDC (estrogen receptor–positive, progesterone receptor–positive, and human epidermal growth factor receptor 2–negative) measuring 1.1 cm in the right breast (arrow). PET/MRI tumor maximum standardized uptake value (SUVmax) was 2.25, tumor mean standardized uptake value (SUVmean) was 1.33, and normal breast SUVmean was 1.16. The PET/CT tumor SUVmax was 1.70, tumor SUVmean was 0.77, and normal breast SUVmean was 1.57. The sequence shown for MRI is the early-phase postcontrast T1-weighted fat-suppressed fast spoiled gradient-echo images.

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Association of ER Status, Histologic Subtype, and Tumor Grade with 18F-FDG Uptake

18F-FDG uptake parameters were higher in grade 3 tumors compared with grade 1 and 2 tumors for both modalities (Table 2). Higher 18F-FDG uptake in ER-negative tumors compared with ER-positive tumors as well as higher 18F-FDG uptake in invasive ductal carcinoma compared with invasive lobular carcinoma in both modalities were observed; however, the differences were not statistically significant (Table 2).

Table 2: Comparison of 18F-FDG Uptake Parameters with Tumor Characteristics

Table 2:

Tumor and Normal Breast 18F-FDG Avidity Measured with PET/MRI Compared with PET/CT

Because the PET/CT acquisition time was 10 minutes, reconstruction of the first 10 minutes of PET/MRI data was performed and compared with the full-length 0–30-minute reconstructed PET/MRI data set. Tumor SUVmax, tumor SUVmean, and tumor SUVmax normalized to contralateral normal breast tissue SUVmean (normSUVmax) were not different between the 0–10-minute and 0–30-minute PET/MRI data sets (Table 3). For subsequent analyses, the 0–10-minute PET/MRI reconstruction was used for a more direct comparison with the 10-minute PET/CT data to minimize differences in total radiopharmaceutical uptake time.

Table 3: Comparison of 18F-FDG Uptake Measured Using 0–10 Minute Versus 0–30 Minute Reconstructed PET/MRI Data

Table 3:

Scatterplots showed that for tumor SUVmax and tumor SUVmean, the uptake values measured using PET/MRI tended to exceed that with PET/CT (Fig 4). Statistical comparison of the tumor uptake parameters measured by the two modalities showed higher tumoral 18F-FDG uptake with PET/MRI SUVmax and SUVmean compared with PET/CT (8.5 ± 1.3 vs 7.3 ± 1.1 [P < .001] and 4.8 ± 0.8 vs 3.7 ± 0.6 [P < .001], respectively) (Table 4). Normal breast SUVmean for PET/MRI versus PET/CT were 1.4 ± 0.09 versus 1.3 ± 0.09 (P = .02), respectively. PET/MRI and PET/CT measurements of tumor 18F-FDG uptake were strongly correlated (rs = 0.95–0.98).

Comparison of tumor fluorine 18 fluorodeoxyglucose (18F-FDG) uptake using breast PET/MRI versus prone PET/CT. Scatterplots for PET/MRI versus PET/CT and line of identity for, A, tumor maximum standardized uptake value (SUVmax), B, tumor mean standardized uptake value (SUVmean), C, tumor SUVmax normalized to normal breast SUVmean (normSUVmax), and, D, tumor SUVmean normalized to normal breast SUVmean (normSUVmean). Spearman rank correlation (rs) with 95% CIs; P < .001 for all.

Figure 4: Comparison of tumor fluorine 18 fluorodeoxyglucose (18F-FDG) uptake using breast PET/MRI versus prone PET/CT. Scatterplots for PET/MRI versus PET/CT and line of identity for, A, tumor maximum standardized uptake value (SUVmax), B, tumor mean standardized uptake value (SUVmean), C, tumor SUVmax normalized to normal breast SUVmean (normSUVmax), and, D, tumor SUVmean normalized to normal breast SUVmean (normSUVmean). Spearman rank correlation (rs) with 95% CIs; P < .001 for all.

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Table 4: Comparison of 18F-FDG Uptake Measured Using PET/MRI versus PET/CT

Table 4:

Measurement differences were reduced when normalizing tumor uptake to normal breast tissue uptake. There was no difference between PET/MRI and PET/CT for normSUVmax (6.3 ± 1.0 vs 6.3 ± 1.1; P = .58) (Table 4).

Measurement Agreement of Tumor 18F-FDG Uptake between PET/MRI and PET/CT

As defined by Bland-Altman analysis, measurement bias for PET/MRI versus PET/CT was +1.12 (95% LoA: −1.98, +4.22) for tumor SUVmax, +1.14 (95% LoA: −1.28, +3.56) for tumor SUVmean, +0.04 (95% LoA: −3.37, +3.44) for the normSUVmax, and +0.37 (95% LoA: −1.51, +2.25) for tumor SUVmean normalized to normal breast SUVmean (normSUVmean) (Fig 5). Measurement bias as a percentage for PET/MRI versus PET/CT was +11.13% (95% LoA: −16.96%, +39.23%) for tumor SUVmax, +24.75% (95% LoA: −6.96%, +56.47%) for tumor SUVmean, +3.86% (95% LoA: −28.92%, +36.64%) for normSUVmax, and +15.69% (95% LoA: −17.33%, +48.70%) for normSUVmean (Fig 5). Thus, normSUVmax was the uptake parameter with the least amount of measurement bias.

Measurement agreement between breast PET/MRI and prone PET/CT. Bland-Altman plots for, A, tumor maximum standardized uptake value (SUVmax), B, tumor mean standardized uptake value (SUVmean), C, tumor SUVmax normalized to normal breast SUVmean (normSUVmax), and, D, tumor SUVmean normalized to normal breast SUVmean (normSUVmean). Left column shows difference between PET/MRI and PET/CT values plotted against the mean of PET/MRI and PET/CT. Right column shows percentage difference plotted against the mean of PET/MRI and PET/CT. The solid y line shows the bias, and the dotted y line shows ± 95% limits of agreement.

Figure 5: Measurement agreement between breast PET/MRI and prone PET/CT. Bland-Altman plots for, A, tumor maximum standardized uptake value (SUVmax), B, tumor mean standardized uptake value (SUVmean), C, tumor SUVmax normalized to normal breast SUVmean (normSUVmax), and, D, tumor SUVmean normalized to normal breast SUVmean (normSUVmean). Left column shows difference between PET/MRI and PET/CT values plotted against the mean of PET/MRI and PET/CT. Right column shows percentage difference plotted against the mean of PET/MRI and PET/CT. The solid y line shows the bias, and the dotted y line shows ± 95% limits of agreement.

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Discussion

The purpose of this study was to develop and test a simultaneous, time-of-flight PET/MRI acquisition protocol specific for breast imaging by comparing tumor 18F-FDG uptake parameters measured with prone breast PET/MRI to prone PET/CT in participants with newly diagnosed primary invasive breast cancer. Strong correlation was demonstrated between tumor uptake values measured with PET/MRI and PET/CT (rs = 0.95–0.98). We observed slightly higher tumor SUVmax, SUVmean, and normSUVmean18F-FDG uptake measured by PET/MRI compared with PET/CT. There was no significant difference between modalities for normSUVmax. The best agreement between PET/MRI and PET/CT measurements was observed with normSUVmax18F-FDG uptake.

Studies comparing the diagnostic performance of conventional supine, whole-body PET/MRI with PET/CT for staging and restaging have shown that PET/MRI performs as well as PET/CT for most malignancies, including breast cancer (45). Additional research focused on semiquantitative analyses of tumor glucose uptake has generally found good correlation between the two modalities; however, several publications have reported statistically significant quantitative differences. Our results with breast PET/MRI were similar to the study published by Al-Nabhani et al which showed that tumor SUVmean was 10% higher with whole-body PET/MRI compared with PET/CT (P < .01) (34). In contrast, other studies have reported higher tumor uptake values measured with PET/CT compared with whole-body PET/MRI. The study published by Drzezga et al included 32 patients, three with breast cancer, and reported higher lesion SUVmean values with PET/CT compared with whole-body PET/MRI (P < .001) (33). Results published by Wiesmüller et al showed that 18F-FDG SUVmax and SUVmean of 94 lesions were 22% and 10% lower, respectively, at whole-body PET/MRI compared with PET/CT (P < .01) in their study of 46 patients, three with breast cancer (35). No significant differences in SUVmax, SUVmean, or metabolic tumor volume between whole-body PET/MRI and PET/CT were found in the 25 primary breast cancers analyzed by Pace et al (36). Similarly, no significant difference in SUVmax (P = .15) or SUVmean (P = .07) between whole-body PET/MRI and PET/CT were found in 31 breast cancer metastases in a study by Pujara et al (37). A study published by Groshar et al, which included 33 patients, 12 with breast cancer, found +7%, +13.9%, and +8.3% mean difference in SUVmax, SUVpeak, and SUVmean, respectively, when comparing PET/CT with whole-body PET/MRI values using Bland-Altman analysis (38).

With the exception of Groshar et al, who randomized the imaging examination order, all of the prior studies were designed with the PET/CT acquisition first followed by PET/MRI. This scan order would be expected to result in increased uptake values measured with PET/MRI because of the longer time for 18F-FDG accumulation in malignancies (46–49). However, this result was not consistently observed in these prior publications, implying that contributing factors beyond scan order and/or uptake time exist. Furthermore, these previous studies used first-generation avalanche photodiode PET detectors without time-of-flight capability and did not use a dedicated breast radiofrequency coil which may contribute to the differences observed with our study.

We found that the 18F-FDG uptake parameter with the least amount of measurement bias (+3.86%) between the two modalities was normSUVmax. Furthermore, the 95% LoA values were −28.92% and +36.64%, which were the closest to clinically acceptable limits of ± 30% based on the PET Response Criteria in Solid Tumors definition for partial response and progressive disease (50). Thus, breast PET/MRI seems to provide an acceptable approximation of tumor glucose uptake as that of PET/CT, the current reference standard. This result raises the possibility that simultaneous breast PET/MRI could be used interchangeably with prone PET/CT for tumor uptake quantification when using normSUVmax and harmonized PET image reconstruction parameters.

With the exception of normSUVmean, our results showed no significant difference in tumor 18F-FDG uptake parameters using data from the first 10 minutes of the breast PET/MRI examination compared with data from the full 30-minute examination. In addition to facilitating a more direct comparison of the PET/MRI data with the 10-minute PET/CT examination, this finding has two important practical implications. First, this implies that the injected dose of 18F-FDG could be reduced which would decrease the overall radiation exposure to the patient. In a study of 26 women with breast cancer who underwent a breast PET/MRI examination using the Signa scanner also used in this study, Sah et al found that a simulated dose reduction of up to 90% resulted in clinically acceptable subjective PET image quality (39). They estimated that a 90% administered dose reduction would result in approximately 0.45-mSv effective dose equivalent radiation exposure for an average patient weighing 75 kg, which is comparable to the 0.44-mSv average effective dose of a digital mammographic examination (51). Second, there is increasing interest in shortening the length of clinical breast MRI examinations. Our data suggest that a 10-minute PET acquisition could be feasibly combined with an abbreviated breast MRI protocol.

The study had some limitations. There was potential selection bias because not all patients with newly diagnosed breast cancer undergo preoperative breast MRI at our institution. Also, participants with large body mass index were not eligible for the study because of limitations in the scanner bore diameter (60 cm). With clinical scheduling constraints beyond our control, the scan order was not randomized which resulted in slightly different 18F-FDG uptake times (approximately 15 minutes). This effect was minimized by directly comparing the first 10-minute acquisition time of the breast PET/MRI with the 10-minute PET/CT examination. To avoid partial volume effects on SUV quantification, participants with tumors smaller than 1 cm were not eligible, which resulted in relatively large tumor sizes in the study cohort.

The results of this work demonstrate that semiquantitative assessment of 18F-FDG uptake of primary invasive breast carcinoma using simultaneous breast PET/MRI provides an acceptable approximation of tumor glucose uptake as does PET/CT, the current reference standard. Measurement differences were minimized between tumor 18F-FDG uptake using breast PET/MRI and prone PET/CT when normalized to normal breast tissue uptake. Establishing the measurement agreement between PET/CT and simultaneous breast PET/MRI for tumor 18F-FDG uptake is an important first step for potentially implementing this new hybrid imaging method for quantitatively assessing the glycolytic activity of primary breast cancer. Furthermore, the MRI component of breast PET/MRI has an added clinical advantage over PET/CT for evaluation of the size and extent of primary tumor enhancement. Further research is warranted to assess the feasibility of using breast PET/MRI to monitor neoadjuvant therapy response.

Disclosures of Conflicts of Interest: A.M.F. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: author paid for virtual lecture (8/21/20) by Wisconsin Association of Hematology and Oncology and Wisconsin Oncology Network Virtual Annual Conference; author receives royalties from Elsevier for book chapters (Diagnostic Imaging: Breast). Other relationships: The Department of Radiology at the University of Wisconsin School of Medicine and Public Health receives research support from GE Healthcare. M.K. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The UW Department of Radiology received research support from GE Healthcare. L.H.B. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The UW Department of Radiology received research support from GE Healthcare. K.S. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The UW Department of Radiology received research support from GE Healthcare. J.M.J. disclosed no relevant relationships. J.K. disclosed no relevant relationships. S.B.P. disclosed no relevant relationships. T.J.B. disclosed no relevant relationships. S.A.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The University of Wisconsin - Madison, Department of Radiology receives research support from GE Healthcare. None of this support was specifically designated to this project or its authors. A.B.M. Activities related to the present article: institution received NIH/NIBIB grant EB026708. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The UW Department of Radiology received research support from GE Healthcare. R.M.S. Activities related to the present article: institution received NIH/NIBIB grant EB026708. Activities not related to the present article: disclosed no relevant relationships. Other relationships: The UW Department of Radiology received research support from GE Healthcare.

Acknowledgments

The authors are grateful to the patients who participated in the study. We also thank Christine Jaskowiak, Kelli Hellenbrand, Timothy Deller, and Frank Korosec for technical support; Molly Naef, Cindy Davis, Meg Bayless, and Jan Yakey for study coordination; and Gemma Gliori and Suzanne Hanson for regulatory compliance.

Author Contributions

Author contributions: Guarantors of integrity of entire study, A.M.F., M.K., R.M.S.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; agrees to ensure any questions related to the work are appropriately resolved, all authors; literature research, A.M.F., M.K., K.S., A.B.M., R.M.S.; clinical studies, A.M.F., M.K., L.H.B., J.M.J., J.K., T.J.B., R.M.S.; experimental studies, M.K., L.H.B., S.B.P., S.A.H., A.B.M.; statistical analysis, A.M.F., M.K., K.S., J.M.J., T.J.B., A.B.M., R.M.S.; and manuscript editing, A.M.F., M.K., L.H.B., K.S., J.K., S.B.P., T.J.B., S.A.H., A.B.M., R.M.S.

Supported by the UW-Madison Department of Radiology, Clinical and Translational Science Award program through the NIH National Center for Advancing Translational Sciences grant 1UL1TR002373, NIH National Institute of Biomedical Imaging and Bioengineering (R01EB026708), and UW Institute of Clinical and Translational Research KL2 Scholar Award (1KL2TR002374).

1 Current address: Consulting Radiologists Ltd, Edina, Minn.

References

  • 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68(6):394–424 [Published correction appears in CA Cancer J Clin 2020;70(4):313.].
    Medline Google Scholar
  • 2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70(1):7–30.
    Medline Google Scholar
  • 3. van Uden DJP, Prins MW, Siesling S, de Wilt JHW, Blanken-Peeters CFJM, Aarntzen EHJG. [18F]FDG PET/CT in the staging of inflammatory breast cancer: A systematic review. Crit Rev Oncol Hematol 2020;151:102943.
    Medline Google Scholar
  • 4. Caresia Aroztegui AP, García Vicente AM, Alvarez Ruiz S, et al. 18F-FDG PET/CT in breast cancer: Evidence-based recommendations in initial staging. Tumour Biol 2017;39(10):1010428317728285.
    Google Scholar
  • 5. Xiao Y, Wang L, Jiang X, She W, He L, Hu G. Diagnostic efficacy of 18F-FDG-PET or PET/CT in breast cancer with suspected recurrence: a systematic review and meta-analysis. Nucl Med Commun 2016;37(11):1180–1188.
    Medline Google Scholar
  • 6. Groheux D. Role of fludeoxyglucose in breast cancer: treatment response. PET Clin 2018;13(3):395–414.
    Medline Google Scholar
  • 7. Ulaner GA. PET/CT for patients with breast cancer: where is the clinical impact? AJR Am J Roentgenol 2019;213(2):254–265.
    Medline Google Scholar
  • 8. Marino MA, Helbich T, Baltzer P, Pinker-Domenig K. Multiparametric MRI of the breast: A review. J Magn Reson Imaging 2018;47(2):301–315.
    Medline Google Scholar
  • 9. Hylton N. Dynamic contrast-enhanced magnetic resonance imaging as an imaging biomarker. J Clin Oncol 2006;24(20):3293–3298.
    Medline Google Scholar
  • 10. Greenwood HI, Freimanis RI, Carpentier BM, Joe BN. Clinical breast magnetic resonance imaging: technique, indications, and future applications. Semin Ultrasound CT MR 2018;39(1):45–59.
    Medline Google Scholar
  • 11. Bitencourt AG, Lima EN, Chojniak R, et al. Multiparametric evaluation of breast lesions using PET-MRI: initial results and future perspectives. Medicine (Baltimore) 2014;93(22):e115.
    Medline Google Scholar
  • 12. Bitencourt AG, Lima EN, Chojniak R, et al. Can 18F-FDG PET improve the evaluation of suspicious breast lesions on MRI? Eur J Radiol 2014;83(8):1381–1386.
    Medline Google Scholar
  • 13. Pinker K, Bogner W, Baltzer P, et al. Improved differentiation of benign and malignant breast tumors with multiparametric 18fluorodeoxyglucose positron emission tomography magnetic resonance imaging: a feasibility study. Clin Cancer Res 2014;20(13):3540–3549.
    Medline Google Scholar
  • 14. Moy L, Noz ME, Maguire GQ Jr, et al. Role of fusion of prone FDG-PET and magnetic resonance imaging of the breasts in the evaluation of breast cancer. Breast J 2010;16(4):369–376.
    Medline Google Scholar
  • 15. Atuegwu NC, Li X, Arlinghaus LR, et al. Longitudinal, intermodality registration of quantitative breast PET and MRI data acquired before and during neoadjuvant chemotherapy: preliminary results. Med Phys 2014;41(5):052302.
    Medline Google Scholar
  • 16. Delso G, Fürst S, Jakoby B, et al. Performance measurements of the Siemens mMR integrated whole-body PET/MR scanner. J Nucl Med 2011;52(12):1914–1922.
    Medline Google Scholar
  • 17. Zaidi H, Ojha N, Morich M, et al. Design and performance evaluation of a whole-body Ingenuity TF PET-MRI system. Phys Med Biol 2011;56(10):3091–3106.
    Medline Google Scholar
  • 18. Grant AM, Deller TW, Khalighi MM, Maramraju SH, Delso G, Levin CS. NEMA NU 2-2012 performance studies for the SiPM-based ToF-PET component of the GE SIGNA PET/MR system. Med Phys 2016;43(5):2334–2343.
    Medline Google Scholar
  • 19. Grueneisen J, Nagarajah J, Buchbender C, et al. Positron emission tomography/magnetic resonance imaging for local tumor staging in patients with primary breast cancer: a comparison with positron emission tomography/computed tomography and magnetic resonance imaging. Invest Radiol 2015;50(8):505–513.
    Medline Google Scholar
  • 20. Margolis NE, Moy L, Sigmund EE, et al. Assessment of aggressiveness of breast cancer using simultaneous 18F-FDG-PET and DCE-MRI: preliminary observation. Clin Nucl Med 2016;41(8):e355–e361.
    Medline Google Scholar
  • 21. Dregely I, Lanz T, Metz S, et al. A 16-channel MR coil for simultaneous PET/MR imaging in breast cancer. Eur Radiol 2015;25(4):1154–1161.
    Medline Google Scholar
  • 22. Aklan B, Paulus DH, Wenkel E, et al. Toward simultaneous PET/MR breast imaging: systematic evaluation and integration of a radiofrequency breast coil. Med Phys 2013;40(2):024301.
    Google Scholar
  • 23. Patrick JC, Terry Thompson R, So A, et al. Technical Note: Comparison of megavoltage, dual-energy, and single-energy CT-based µ-maps for a four-channel breast coil in PET/MRI. Med Phys 2017;44(9):4758–4765.
    Medline Google Scholar
  • 24. Botsikas D, Kalovidouri A, Becker M, et al. Clinical utility of 18F-FDG-PET/MR for preoperative breast cancer staging. Eur Radiol 2016;26(7):2297–2307.
    Medline Google Scholar
  • 25. Goorts B, Vöö S, van Nijnatten TJA, et al. Hybrid 18F-FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging 2017;44(11):1796–1805.
    Medline Google Scholar
  • 26. Taneja S, Jena A, Goel R, Sarin R, Kaul S. Simultaneous whole-body 18F-FDG PET-MRI in primary staging of breast cancer: a pilot study. Eur J Radiol 2014;83(12):2231–2239.
    Medline Google Scholar
  • 27. Romeo V, D’Aiuto M, Frasci G, Imbriaco M, Nicolai E. Simultaneous PET/MRI assessment of response to cytotoxic and hormone neo-adjuvant chemotherapy in breast cancer: a preliminary report. Med Oncol 2017;34(2):18.
    Medline Google Scholar
  • 28. Jena A, Taneja S, Singh A, et al. Association of pharmacokinetic and metabolic parameters derived using simultaneous PET/MRI: Initial findings and impact on response evaluation in breast cancer. Eur J Radiol 2017;92:30–36.
    Medline Google Scholar
  • 29. Wang J, Shih TT, Yen RF. Multiparametric evaluation of treatment response to neoadjuvant chemotherapy in breast cancer using integrated PET/MR. Clin Nucl Med 2017;42(7):506–513.
    Medline Google Scholar
  • 30. Cho N, Im SA, Cheon GJ, et al. Integrated 18F-FDG PET/MRI in breast cancer: early prediction of response to neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging 2018;45(3):328–339.
    Medline Google Scholar
  • 31. Kinahan PE, Perlman ES, Sunderland JJ, et al. The QIBA Profile for FDG PET/CT as an imaging biomarker measuring response to cancer therapy. Radiology 2020;294(3):647–657.
    Medline Google Scholar
  • 32. Paulus DH, Quick HH. Hybrid positron emission tomography/magnetic resonance imaging: challenges, methods, and state of the art of hardware component attenuation correction. Invest Radiol 2016;51(10):624–634.
    Medline Google Scholar
  • 33. Drzezga A, Souvatzoglou M, Eiber M, et al. First clinical experience with integrated whole-body PET/MR: comparison to PET/CT in patients with oncologic diagnoses. J Nucl Med 2012;53(6):845–855.
    Medline Google Scholar
  • 34. Al-Nabhani KZ, Syed R, Michopoulou S, et al. Qualitative and quantitative comparison of PET/CT and PET/MR imaging in clinical practice. J Nucl Med 2014;55(1):88–94.
    Medline Google Scholar
  • 35. Wiesmüller M, Quick HH, Navalpakkam B, et al. Comparison of lesion detection and quantitation of tracer uptake between PET from a simultaneously acquiring whole-body PET/MR hybrid scanner and PET from PET/CT. Eur J Nucl Med Mol Imaging 2013;40(1):12–21.
    Medline Google Scholar
  • 36. Pace L, Nicolai E, Luongo A, et al. Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: lesion detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal organ tissues. Eur J Radiol 2014;83(2):289–296.
    Medline Google Scholar
  • 37. Pujara AC, Raad RA, Ponzo F, et al. Standardized uptake values from PET/MRI in metastatic breast cancer: an organ-based comparison with PET/CT. Breast J 2016;22(3):264–273.
    Medline Google Scholar
  • 38. Groshar D, Bernstine H, Goldberg N, et al. Reproducibility and repeatability of same-day two sequential FDG PET/MR and PET/CT. Cancer Imaging 2017;17(1):11.
    Medline Google Scholar
  • 39. Sah BR, Ghafoor S, Burger IA, et al. Feasibility of 18F-FDG dose reductions in breast cancer PET/MRI. J Nucl Med 2018;59(12):1817–1822.
    Medline Google Scholar
  • 40. D’Orsi CJ, Sickles EA, Mendelson EB, Morris EA. ACR BI-RADS Atlas, Breast Imaging Reporting and Data System. 5th ed. Reston, Va: American College of Radiology, 2013.
    Google Scholar
  • 41. Bettinardi V, Presotto L, Rapisarda E, Picchio M, Gianolli L, Gilardi MC. Physical performance of the new hybrid PET⁄CT Discovery-690. Med Phys 2011;38(10):5394–5411.
    Medline Google Scholar
  • 42. Bonett DG, Wright TA. Sample size requirements for estimating pearson, kendall and spearman correlations. Psychometrika 2000;65(1):23–28.
    Google Scholar
  • 43. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1(8476):307–310.
    Medline Google Scholar
  • 44. Kottner J, Audigé L, Brorson S, et al. Guidelines for reporting reliability and agreement studies (GRRAS) were proposed. J Clin Epidemiol 2011;64(1):96–106.
    Medline Google Scholar
  • 45. Spick C, Herrmann K, Czernin J. 18F-FDG PET/CT and PET/MRI perform equally well in cancer: evidence from studies on more than 2,300 patients. J Nucl Med 2016;57(3):420–430.
    Medline Google Scholar
  • 46. Kumar R, Loving VA, Chauhan A, Zhuang H, Mitchell S, Alavi A. Potential of dual-time-point imaging to improve breast cancer diagnosis with (18)F-FDG PET. J Nucl Med 2005;46(11):1819–1824.
    Medline Google Scholar
  • 47. Boerner AR, Weckesser M, Herzog H, et al. Optimal scan time for fluorine-18 fluorodeoxyglucose positron emission tomography in breast cancer. Eur J Nucl Med 1999;26(3):226–230.
    Medline Google Scholar
  • 48. Wangerin KA, Muzi M, Peterson LM, et al. Effect of 18F-FDG uptake time on lesion detectability in PET imaging of early stage breast cancer. Tomography 2015;1(1):53–60.
    Medline Google Scholar
  • 49. Imbriaco M, Caprio MG, Limite G, et al. Dual-time-point 18F-FDG PET/CT versus dynamic breast MRI of suspicious breast lesions. AJR Am J Roentgenol 2008;191(5):1323–1330.
    Medline Google Scholar
  • 50. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med 2009;50(Suppl 1):122S–150S.
    Medline Google Scholar
  • 51. Hendrick RE. Radiation doses and cancer risks from breast imaging studies. Radiology 2010;257(1):246–253.
    Google Scholar

Article History

Received: July 1 2020
Revision requested: Aug 26 2020
Revision received: Sept 24 2020
Accepted: Oct 28 2020
Published online: Jan 15 2021