Prospective comparison of synthetic high b-value field of view optimized and constrained undistorted multiplexed sensitivity encoding (FOCUS-MUSE) and FOCUS diffusion-weighted imaging in evaluating cervical cancer
Original Article

Prospective comparison of synthetic high b-value field of view optimized and constrained undistorted multiplexed sensitivity encoding (FOCUS-MUSE) and FOCUS diffusion-weighted imaging in evaluating cervical cancer

Wancui Mei1#, Chengcheng Li2#, Qian Tang3, Ling Sang1, Sai Wang1, Qiqi Zhou1, Lin Xu1, Weiyin Vivian Liu4*, Wen Chen1*

1Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, China; 2Department of Ultrasound, Taihe Hospital, Hubei University of Medicine, Shiyan, China; 3Department of Radiology, Minda Hospital, Hubei Minzu University, Enshi, China; 4GE Healthcare, MR Research, Beijing, China

Contributions: (I) Conception and design: W Mei, C Li; (II) Administrative support: WV Liu, W Chen; (III) Provision of study materials or patients: W Mei, C Li, L Sang; (IV) Collection and assembly of data: W Mei, Q Tang, L Sang, S Wang, Q Zhou; (V) Data analysis and interpretation: W Mei, C Li, L Xu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work.

*These authors contributed equally to this work as co-senior authors.

Correspondence to: Weiyin Vivian Liu, MD. GE Healthcare, MR Research, No. 1 Yongchang North Road, Beijing Economic and Technological Development Zone, Beijing 100176, China. Email: lanny.320@163.com; Wen Chen, MD, PhD. Department of Radiology, Taihe Hospital, Hubei University of Medicine, No. 32 Renmin South Rd., Maojian District, Shiyan 442000, China. Email: taiheren007@163.com.

Background: Cervical cancer affects women’s health worldwide. Accurate diagnosis based on the International Federation of Obstetrics and Gynecology (FIGO) is crucial for selecting treatment strategies for cervical cancer. Compared to conventional diffusion-weighted imaging (DWI) with a b-value of 800 s/mm2, using b-values higher than 1,000 s/mm2 can effectively reduce T2 effects, increase contrast between tumors and normal tissues, and thus improve the diagnostic reliability of malignant tumors. However, direct acquisition of high b-value DWI typically requires longer scanning time and a relatively lower signal-to-noise ratio (SNR). The synthetic high b-value DWI (syDWI) generated by fitting signal attenuation curves of 2 to 5 different b-values can avoid the drawbacks of actual scanning of high b-value images and obtain higher image quality without additional scanning time. Its accuracy in tumor detection and diagnosis is superior or comparable to that of actual scanning of high b-value DWI. The aim of the study was to explore the feasibility of synthetic high-b-value field of view optimized and constrained undistorted multiplexed sensitivity encoding diffusion-weighted imaging (FOCUS-MUSE DWI) in diagnosing cervical cancer using FOCUS DWI as reference.

Methods: A total of 55 patients with cervical cancer and 33 volunteers prospectively underwent FOCUS-MUSE DWI and FOCUS DWI with a 5b-protocol: b =0, 100, 400, 800, 1,200 s/mm2. Two experienced radiologists conducted subjective and objective evaluation on sFOCUS-MUSE DWIb =800, sFOCUS DWIb =800, syFOCUS-MUSE DWIb =1,500, and syFOCUS DWIb =1,500 as well as measured corresponding apparent diffusion coefficient (ADC) values. Inter-reader agreements of subjective and objective assessment were analyzed respectively using interclass correlation coefficient (ICC) and kappa statistics; comparison of image quality and ADC values was carried out using paired t-test, Wilcoxon signed rank test, or Mann Whitney U; and diagnostic efficiency was calculated using receiver operating characteristic (ROC) curve.

Results: The sFOCUS-MUSE DWIb =800 and syFOCUS-MUSE DWIb =1,500 had higher subjective image quality (susceptibility artifacts, geometric distortion, anatomy details, and overall image quality) but lower SNR than sFOCUS DWIb =800 and syFOCUS DWIb =1,500 (all P<0.001). In the pooled cohort of patients and healthy volunteers (n=88), FOCUS-MUSE DWI generated significantly lower ADC values than conventional FOCUS at both b-values (b =800 s/mm2, P=0.025; b =1,500 s/mm2, P=0.001). The late-stage group (IIB–IV) showed lower ADC values than the early-stage group (IB–IIA) and healthy controls using each scanned and synthetic DWIs (all P<0.001). FOCUS-MUSE-syADCb =1,500 had equivalent AUCs to FOCUS-MUSE-syADCb =1,500, FOCUS-sADCb =800, and FOCUS-syADCb =800.

Conclusions: FOCUS-MUSE DWI provides better image quality for evaluating cervical cancer and well diagnostic performance than FOCUS DWI. Synthetic high-b-value FOCUS-MUSE DWI takes no additional scan time and offers syADC values with reliable discrimination ability of cervical cancer with different FIGO stages.

Keywords: Cervical cancer; magnetic resonance imaging (MRI); diffusion-weighted imaging (DWI); synthetic diffusion-weighted imaging

Submitted Feb 11, 2025. Accepted for publication Jul 14, 2025. Published online Sep 18, 2025.

doi: 10.21037/qims-2025-338

Introduction

Both the morbidity and mortality of cervical cancer rank fourth among cancers affecting women (1). Early diagnosis of International Federation of Obstetrics and Gynecology (FIGO) stage for cervical cancer is essential for strategic treatment planning (2). With the features of high spatial resolution, sensitivity, and specificity in tumor detection (3), magnetic resonance imaging (MRI) assists gynecologists in the preoperative staging of cervical cancer (4). Diffusion-weighted imaging (DWI) combined with quantitative apparent diffusion coefficient (ADC) can identify the pathological features of cervical cancer and evaluate tumor invasion extent and treatment responses (5,6).

A variety of DWI technologies are available in clinics, including single-shot echo planar imaging DWI, PROPELLER/BLADE DWI, reduced field-of-view single-shot DWI (rFOV DWI; FOCUS in GE, Zoomit in Siemens, Zoom in Philips), multi-shot DWI (MUSE in GE, RESOLVE in Siemens, and IRIS in Philips), and field of view optimized and constrained undistorted multiplexed sensitivity encoding diffusion-weighted imaging (FOCUS-MUSE DWI) (a requestable work-in-progress sequence at present). The rFOV and multi-shot DWIs may reduce magnetic sensitivity and motion artifacts while increasing image resolution (7,8). The former is used via simultaneous two-dimensional (2D) spatially-selective radiofrequency (2D RF) pulse and 180° refocusing pulse (5,9), whereas the latter is performed through at least two separate RF excitations followed by alternative k-space fill-in (7,10). The last three types of DWIs have reported good image quality and diagnostic efficacy on pancreas (7), breast (8), uterus (11), and prostate (12). MUSE DWI has better image quality than FOCUS DWI and nearly equivalent diagnostic performance to dynamic contrast-enhanced (DCE)-MRI in assessing superficial and deep myographic infiltration of endometrial cancer (EC) (11). FOCUS-MUSE DWI provides more reliable pancreatic image quality and ADC measurements than FOCUS DWI and equivalent objective assessment but superior subjective evaluation to MUSE DWI (7). Moreover, it provides better images to evaluate thyroid-associated ophthalmopathy and lung lesions (13,14).

DWI with a b-value of lower than 1,000 s/mm2 is mostly used in clinical diagnosis of cervical diseases (15,16) as hyperintensity in the endocervical canal may incorrectly evaluate extent of tumor invasion (17). DWI with a b-value greater than 1,000 s/mm2 in prostate (18), pancreas (19), and breast (20) effectively reduces T2 transmission effect and increases tumor-to-tissue contrasts. Compared to DWIs with conventional b-value (800 s/mm2), DWI with ultra-high b-value (2,000 s/mm2) has better background suppression for higher diagnostic reliability of cervical cancer despite more apparent object distortion (21). However, high b-value DWI takes a longer scanning time, lending itself to patient discomfort and more respiratory motion artifacts (22). Despite improved assessment of cervical paraventricular invasion on a scanned high-b-value DWI superimposed on T2-weighted imaging (23), synthetic high-b-value DWIs have less motion artifacts and image distortion than scanned ones (19). A reliable synthetic high b-value DWI is generated by fitting a signal decay curve with 2–5 different b-values (24) and applications in prostate (25), pancreas (19), and uterus (26) have shown better image quality and superior or equivalent diagnostic accuracy of tumor detection to those of scanned DWI without additional scan time. In a uterus 1.5 T MRI study of synthetic FOCUS DWI (syFOCUS DWI), 5b-protocol syFOCUS DWIs with b-values of 1,200 and 1,500 s/mm2 have shown image quality and diagnosis as good as 13b-protocol ones, and both synthetic DWIs had better subjective assessment than actual scanned ones (26).

An ADC map assists the assessment of FIGO stage for cervical cancer (16). Synthetic high-b-value DWIs together with an ADC map have been shown to have a good agreement on actually-scanned high-b-value DWIs for liver, spleen, muscle, and lesion mass (27). Therefore, this study aimed to explore the feasibility and diagnostic efficacy of 5b-protocol-generated high-b-value syFOCUS-MUSE DWI in cervical cancer. Meanwhile, the diagnostic efficacy of ADC maps with either b =1,500 s/mm2 or b =800 s/mm2 was examined to confirm its clinical values. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-338/rc).

Methods

Participants

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and approved by the Ethics Review Committee of Taihe Hospital, Shiyan City (IRB No. 2024KS11). All participants in the study have provided written informed consent. A total of 55 patients with cervical cancer and 33 healthy volunteers were prospectively recruited from February 2023 to September 2023. The inclusion criteria were as follows: (I) cervical cancer confirmed by biopsy; (II) no previous surgery, radiotherapy, and chemotherapy; (III) complete MRI examinations. The exclusion criteria were as follows: (I) incomplete pathological data; (II) poor image quality and obvious motion artifacts; (III) rare histological subtypes and other malignancies and complications; (IV) invisible lesions on magnetic resonance (MR) images (Figure 1).

Figure 1 Flowchart of patient inclusion and exclusion. Patients were diagnosed according to the FIGO, 2018 and classified into the early-stages group (stage IB–IIA) and the late-stages group (stage IIB–IV). Histological subtypes include SCC and ACA. ACA, adenocarcinoma; FIGO, International Federation of Obstetrics and Gynecology; FOCUS DWI, field of view optimized and constrained undistorted single-shot diffusion-weighted imaging; FOCUS-MUSE, field of view optimized and constrained undistorted multiplexed sensitivity encoding; MRI, magnetic resonance imaging; SCC, squamous cell carcinoma.

MRI examination and data post-processing

All enrolled patients underwent MRI examinations on a 3.0 T scanner (Signa Architect, GE Healthcare, Chicago, IL, USA) using a 16-channel phase-array body coil and a built-in 40-channel bed spine coil. The MRI protocol contains routine sequences such as T2-weighted imaging (T2WI), FOCUS DWI, and FOCUS-MUSE DWI sequences [repetition time (TR) =4,500 ms, echo time (TE) =80.7 (FOCUS)/88.5 (FOCUS-MUSE) ms, thickness =4 mm, field of view (FOV) =22×18 cm2, matrix =110×92; two multiple b-value schemes: 5b-value scheme for FOCUS DWI and FOCUS-MSUE DWI, b =0, 100, 400, 800, 1,200 s/mm2; number of excitations (NEX) =1 for b ≤200, NEX =2 for b >200; scan time: 3 minutes, 3 seconds and 3 minutes]. Synthetic DWIs with b-value of 1,500 s/mm2 were automatically generated without additional scan time once the corresponding sequence scan was completed. ADC maps were post-processed on GE Advanced Workstation 4.7 and computed using two b-values (one scanned DWI with b =0, the other b =800/1,500 s/mm2 of scanned or synthetic DWI) including scanned ADC maps (FOCUS-MUSE-sADCb =800, FOCUS-sADCb =800) and synthetic ones (FOCUS-MUSE-syADCb =1,500, FOCUS-syADCb =1,500).

Subjective image quality analysis

Using axial T2WI images as reference, qualitative image analysis was performed by two radiologists with at least 10 years of diagnosis experience in pelvic imaging. FOCUS-MUSE DWI and FOCUS DWI images of all 55 patients were independently evaluated using a 4-point Likert scale at five aspects [susceptibility artifacts (4= excellent, 3= good, 2= fair, 1= poor); geometric deformity (4= no, 3= mild, 2= severe, 1= severe); anatomy details (4= excellent, clear outline, 3= good, small part of the outline is not clear, 2= average, most part of the outline is not clear, 1= poor, not identifiable)]; overall image quality (4= excellent, 3= good, 2= fair, 1= poor).

Objective image quality analysis

Two experienced radiologists were double-blinded to image information and plotted regions of interest (ROIs; area: 50±5 mm2) on DW images with b-value of 800 and 1,500 s/mm2, and then copied and pasted them onto the rest of the corresponding DWI images. The mean signal strength (SI) and standard deviation (SD) of lesion (lesion), gluteus maximus (tissue) and subcutaneous fat (background) were measured. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated as follows:

SNR=SIlesion/SDbackground

CNR=(SIlesion−SItissue)/SDlesion2+SDtissue2

Quantitative assessment

Three ROIs with areas of 50±5 mm2 were manually drawn on the maximum lesion or cervical cross-section of DWI images with b =800 and 1,500 s/mm2 in avoidance of visible blood vessels, tumors, bleeding, and necrosis, and then copied to the corresponding ADC maps to retrieve ADC values. The diagnostic efficacy of all ADC-derived values was analyzed using receiver operating characteristic (ROC) curves for comparisons between cervical cancer patients and healthy volunteers, the early-stage group (IB–IIA) and healthy group, and the early-stage group (IB–IIA) and late-stage group (IIB–IV).

Statistical analysis

All statistical analyses were performed using the software SPSS 27.0 (IBM Corp., Armonk, NY, USA) and MedCalc version 19.8.0 (MedCalc Software BVBA, Ostend, Belgium). Data presentation in mean ± SD and median (minimum, maximum) respectively depended on whether the data did or did not conform to normal distribution and equal variance according to Levene test and Shapiro-Wilk test. Inter-observer and inter-modality agreement of subjective image quality were measured using weighted kappa statistics; objective image quality was assessed using the interclass correlation coefficient (ICC). The kappa and ICC values were interpreted as follows: 0.00–0.20, poor agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate agreement; 0.61–0.80, good agreement; 0.81–1.00, excellent agreement. Subjective and objective scores and ADC were compared using paired t-test, Wilcoxon signed test, or Mann-Whitney U according to homoscedasticity and normality. The area under the ROC curve (AUC) was used to analyze diagnostic performance for any two groups (controls vs. patients, controls vs. early-stage group, early-stage group vs. late-stage group). A P value <0.05 was considered statistically significant.

Results

Clinical characteristics

Between February 2023 and September 2023, 55 patients (mean age, 55.74±10.29 years; age range, 29–74 years) and healthy volunteers (mean age, 52.71±6.64 years; age range, 33–66 years) were enrolled in this study. Of all 55 patients, the FIGO stages of the patients included IB (n=18), IIA (n=8), IIB (n=9), III (n=14), and IV (n=6). The age differences between the patient group and the early FIGO (IB–IIA) group compared to the healthy group were not statistically significant (P=0.10, P=0.29).

Inter-observer and inter-modality agreement of image quality

Table 1 shows that the inter-reader agreement of image quality assessed by 4-point Likert scores for sFOCUS-MUSEb =800, sFOCUSb =800, syFOCUS-MUSEb =1,500, and syFOCUSb =1,500 were good to strong (0.732–0.942) and the inter-modality difference of image quality between FOCUS-MUSE and FOCUS DWI. Table 2 also presents with good to excellent inter-reader consistency of SNR and CNR measurements of sFOCUS-MUSEb =800, sFOCUSb =800, syFOCUS-MUSEb =1,500, and syFOCUSb =1,500, with the ICC value ranging from 0.791 to 0.971, respectively.

Table 1

Inter-reader consistency of subjective evaluation for scanned and synthetic DWIs and comparisons of subjective evaluation of scanned and synthetic DWIs

Parameters Sequences Sequences
sFOCUS-MUSEb =800 sFOCUSb =800 P value syFOCUS-MUSEb =1,500 syFOCUSb =1,500 P value
Susceptibility artifacts
   Reader 1 4 (2, 4) 3 (2, 4) <0.001 4 (2, 4) 3 (2, 4) <0.001
   Reader 2 4 (2, 4) 3 (2, 4) <0.001 4 (2, 4) 3 (2, 4) <0.001
   Kappa 0.877 0.942 0.732 0.831
Geometric distortion
   Reader 1 4 (2, 4) 3 (2, 3) <0.001 4 (2, 4) 3 (2, 4) <0.001
   Reader 2 4 (2, 4) 3 (2, 3) <0.001 4 (2, 4) 3 (2, 4) <0.001
   Kappa 0.869 0.923 0.889 0.896
Anatomy details
   Reader 1 4 (3, 4) 2 (1, 3) <0.001 4 (3, 4) 3 (1, 4) <0.001
   Reader 2 4 (3, 4) 2 (1, 3) <0.001 4 (3, 4) 3 (1, 3) <0.001
   Kappa 0.824 0.930 0.770 0.896
Overall image quality
   Reader 1 4 (2, 4) 2 (2, 3) <0.001 4 (2, 4) 3 (2, 4) <0.001
   Reader 2 4 (2, 4) 2 (2, 3) <0.001 4 (2, 4) 2 (2, 4) <0.001
   Kappa 0.871 0.890 0.835 0.824

Data are reported as median (min, max) unless otherwise stated. P value <0.05 was considered statistically significant. DWI, diffusion-weighted imaging; FOCUS-MUSE, field of view optimized and constrained undistorted multiplexed sensitivity encoding; sFOCUS-MUSE, scanned FOCUS-MUSE DWI; syFOCUS-MUSE, synthetic FOCUS-MUSE DWI.

Table 2

Inter-reader consistency of SNR and CNR for scanned and synthetic DWIs

Parameters Sequences Sequences
sFOCUS-MUSEb =800 sFOCUSb =800 P value syFOCUS-MUSEb =1,500 syFOCUSb =1,500 P value
SNR
   Reader 1 27.95±7.07 37.81±11.45 <0.001 23.79±6.88 34.15±10.78 <0.001
   Reader 2 28.05±7.32 37.24±9.95 <0.001 22.75±6.52 32.70±10.76 <0.001
   ICC 0.792 0.932 0.829 0.800
CNR
   Reader 1 0.80±0.04 0.80±0.05 0.867 0.81±0.04 0.83±0.06 0.075
   Reader 2 0.80±0.04 0.80±0.05 0.610 0.81±0.05 0.83±0.06 0.088
   ICC 0.840 0.971 0.882 0.856

Data are reported as mean ± standard deviation unless otherwise stated. P value <0.05 was considered statistically significant. ICC, interclass correlation coefficient; CNR, contrast-to-noise ratio; DWI, diffusion-weighted imaging; FOCUS-MUSE, field of view optimized and constrained undistorted multiplexed sensitivity encoding; sFOCUS-MUSE, scanned FOCUS-MUSE DWI; SNR, signal-to-noise ratio; syFOCUS-MUSE, synthetic FOCUS-MUSE DWI.

Subjective and objective image quality scores

syFOCUS-MUSEb =1,500 and sFOCUS-MUSEb =800 respectively showed significantly higher scores at susceptibility artifacts, geometric distortion, anatomy details, and overall image quality than did syFOCUSb =1,500 and sFOCUSb =800 (both P<0.001, Table 1 and Figure 2). Accordingly, sFOCUSb =800 and syFOCUSb =1,500 had significantly higher SNR than sFOCUS-MUSEb =800 and syFOCUS-MUSEb =1,500 (34.15±10.78 vs. 27.95±7.07, 32.70±10.76 vs. 18.48±5.21; all P<0.001, Table 2 and Figure 3). No significantly different CNRs were found between sFOCUS-MUSEb =800 and sFOCUSb =800 as well as syFOCUS-MUSEb =1,500 and syFOCUSb =1,500 (0.80±0.04 vs. 0.80±0.05, 0.81±0.04 vs. 0.83±0.06).

Figure 2 Representative cases demonstrating image quality differences between FOCUS and FOCUS-MUSE DWI. Case 1: a 56-year-old female with FIGO IIB stage cervical SCC, as indicated by the arrow. (A) sFOCUSb =800 and (C) syFOCUSb =1,500 presented obscure anatomical details; (B) sFOCUS-MUSEb =800 and (D) syFOCUS-MUSEb =1,500 demonstrated clear rectal-uterine boundaries. Case 2: a 48-year-old female with FIGO stage IIIA SCC, as indicated by the arrow. (E) sFOCUSb =800 and (G) syFOCUSb =1,500 presented obvious rectal-uterine geometric distortion; (F) sFOCUS-MUSEb =800 and (H) syFOCUS-MUSEb =1,500 displayed improved geometric fidelity. Case 3: a 53-year-old female with FIGO stage IIIA SCC, as indicated by the arrow. (I) sFOCUSb =800 and (K) syFOCUSb =1,500 presented artifact with regional signal enhancement and distortion; (J) sFOCUS-MUSEb =800 and (L) syFOCUS-MUSEb =1,500 displayed less artifact without distortion. FIGO, International Federation of Obstetrics and Gynecology; FOCUS DWI, field of view optimized and constrained undistorted single-shot diffusion-weighted imaging; FOCUS-MUSE DWI, field of view optimized and constrained undistorted multiplexed sensitivity encoding diffusion-weighted imaging; SCC, squamous cell carcinoma; sFOCUS-MUSE, scanned FOCUS-MUSE DWI; syFOCUS-MUSE, synthetic FOCUS-MUSE DWI.
Figure 3 Comparisons of SNR and CNR of scanned and synthetic DWIs. (A) Comparisons for SNR measurands on sFOCUS-MUSEb =800 and sFOCUSb =800. (B) Comparisons for SNR measurands on syFOCUS-MUSEb =1,500 and syFOCUSb =1,500. (C) Comparisons for CNR measurands on sFOCUS-MUSEb =800 and sFOCUSb =800. (D) Comparisons for CNR measurands on syFOCUS-MUSEb =1,500 and syFOCUSb =1,500. *, P>0.05; **, P<0.05. CNR, contrast-to-noise ratio; DWI, diffusion-weighted imaging; FOCUS DWI, field of view optimized and constrained undistorted single-shot diffusion-weighted imaging; FOCUS-MUSE DWI, field of view optimized and constrained undistorted multiplexed sensitivity encoding diffusion-weighted imaging; sFOCUS-MUSE, scanned FOCUS-MUSE DWI; SNR, signal-to-noise ratio; syFOCUS-MUSE, synthetic FOCUS-MUSE DWI.

Quantitative assessment

FOCUS-MUSE and conventional FOCUS sequences presented no significantly different ADC values for the healthy group, early-stage group, and late-stage group at either b-value (b =800 s/mm2, P=0.278, 0.125, 0.455; b =1,500 s/mm2, P=0.241, 0.300, 0.058; Table 3). In the pooled cohort of patients and healthy volunteers (n=88), FOCUS-MUSE sequences demonstrated significantly lower ADC values compared to conventional FOCUS at both b-values (b =800 s/mm2, P=0.025; b=1,500 s/mm2, P=0.001). Moreover, sFOCUS-MUSEb =800, sFOCUSb =800, syFOCUS-MUSEb =1,500, and syFOCUSb =1,500 showed statistically decreasing ADC values in the healthy group (1.96±0.25, 2.01±0.28, 1.59±0.17, 1.64±0.24) followed by the early-stage group (IB–IIA) (1.02±0.17, 1.09±0.35, 0.94±0.23, 0.96±0.25) and late-stage group (IIB–IV) (0.77±0.11, 0.78±0.11, 0.71±0.09, 0.74±0.08; all P<0.001, Table 3 and Figure 4). ADC values respectively computed by b-values of 0 and 800 or 1,500 s/mm2 were shown to be able to distinguish between benign and malignant cervical tumors, the early and late cervical tumors, and CC with different FIGO stages (P<0.001, Table 4 and Figure 5). FOCUS-MUSE-syADCb =1,500 had equivalent diagnostic efficacy on identifying cervical tumors, differentiating the early-stage group from the healthy group, and staging with AUC of 0.992, 0.984, and 0.889 higher than FOCUS-MUSE-sADCb =800 (AUC =0.990, 0.979, 0.886), FOCUS-sADCb =800 (0.981, 0.960, 0.789), and FOCUS-syADCb =1,500 (0.981, 0.961, 0.852).

Table 3

Comparison of ADC (×10−3 mm2/s) between the two DWI techniques in healthy controls and cervical cancer patients

Participants Sequences Sequences
sFOCUS-MUSEb =800 sFOCUSb =800 P value syFOCUS-MUSEb =1,500 syFOCUSb =1,500 P value
Healthy controls (n=33) 1.96±0.25 2.01±0.28 0.278 1.59±0.17 1.64±0.24 0.214
Early-stage group (IB–IIA) (n=26) 1.02±0.17 1.09±0.35 0.125 0.94±0.23 0.96±0.25 0.300
Late-stage group (IIB–IV) (n=29) 0.77±0.11 0.78±0.11 0.455 0.71±0.09 0.74±0.08 0.058
   P value <0.001 <0.001 <0.001 <0.001
Healthy controls and patients (n=88) 1.29±0.56 1.34±0.61 0.025 1.11±0.42 1.14±0.45 0.001

Data are reported as mean ± standard deviation. P value <0.05 was considered statistically significant. ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; FOCUS-MUSE, field of view optimized and constrained undistorted multiplexed sensitivity encoding; sFOCUS-MUSE, scanned FOCUS-MUSE DWI; syFOCUS-MUSE, synthetic FOCUS-MUSE DWI.

Figure 4 Comparisons of ADC values measured among healthy controls, patients with early-stage group (IB–IIA), and those with late-stage group (IIB–IV). (A) ADC values measured on sFOCUS-MUSEb =800. (B) ADC values measured on sFOCUSb =800. (C) ADC values measured on syFOCUS-MUSEb =1,500. (D) ADC values measured on syFOCUSb =1,500. **, P<0.05. ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; FOCUS-MUSE DWI, field of view optimized and constrained undistorted multiplexed sensitivity encoding diffusion-weighted imaging, sFOCUS-MUSE, scanned FOCUS-MUSE DWI; syFOCUS-MUSE, synthetic FOCUS-MUSE DWI.

Table 4

Diagnostic efficacy of ADC values using FOCUS-MUSE and FOCUS DWIs on differentiating the patients with cervical cancer from the normal controls, the early stage of cervical cancer from the normal controls and the early stage of cervical cancer from the late one

Parameters AUC (95% CI) Sensitivity (%) Specificity (%) P value Cut-off value (×10−3 mm2/s)
Cervical cancer from the normal controls
   FOCUS-MUSE-sADCb =800 0.990 (0.975–1.000) 96.9 96.3 <0.001 1.615
   FOCUS-sADCb =800 0.981 (0.954–1.000) 96.9 94.5 <0.001 1.560
   FOCUS-MUSE-syADCb =1,500 0.992 (0.980–1.000) 100.0 96.3 <0.001 1.375
   FOCUS-syADCb =1,500 0.981 (0.961–1.000) 100.0 87.2 <0.001 0.990
The early stage of cervical cancer from the normal controls
   FOCUS-MUSE-sADCb =800 0.979 (0.949–1.000) 96.9 92.3 <0.001 1.615
   FOCUS-sADCb =800 0.960 (0.904–1.000) 93.9 92.3 <0.001 1.610
   FOCUS-MUSE-syADCb =1,500 0.984 (0.959–1.000) 100.0 92.3 <0.001 1.375
   FOCUS-syADCb =1,500 0.961 (0.920–1.000) 81.8 96.1 <0.001 1.525
The early stage of cervical cancer from the late one
   FOCUS-MUSE-sADCb =800 0.886 (0.800–0.965) 79.3 96.1 <0.001 0.865
   FOCUS-sADCb =800 0.789 (0.664–0.913) 71.4 76.9 <0.001 0.785
   FOCUS-MUSE-syADCb =1,500 0.889 (0.814–0.969) 80.7 98.6 <0.001 0.805
   FOCUS-syADCb =1,500 0.852 (0.744–0.960) 65.3 96.5 <0.001 0.855

P value <0.05 was considered statistically significant. AUC, area under the receiver operating characteristic curve; CI, confidence interval; FOCUS DWI, field of view optimized and constrained undistorted single-shot diffusion-weighted imaging; FOCUS-MUSE, field of view optimized and constrained undistorted multiplexed sensitivity encoding; sADC, scanned apparent diffusion coefficient; syADC, synthetic apparent diffusion coefficient.

Figure 5 The ROC curves of ADC values for distinguishing. (A) patients with cervical cancer from the normal controls, (B) patients with the early stage of cervical cancer from the normal controls as well as (C) patients with the early stage of cervical cancer from those with the late one using scanned and synthetic FOCUS-MUSE and FOCUS DWIs respectively with b-values of 800 and 1,500 s/mm2. ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; FOCUS DWI, field of view optimized and constrained undistorted single-shot diffusion-weighted imaging; FOCUS-MUSE DWI, field of view optimized and constrained undistorted multiplexed sensitivity encoding diffusion-weighted imaging; ROC, receiver operating characteristic; sFOCUS-MUSE, scanned FOCUS-MUSE DWI; syFOCUS-MUSE, synthetic FOCUS-MUSE DWI.

Discussion

We firstly showed that synthetic FOCUS-MUSEb =1,500 and calculated ADCb =1,500 had a great potential in better differentiation of cervical cancer according to clinicopathological characteristics of CC from normal tissues with an AUC of 0.981–0.992 using FOCUS-DWI as a reference. In particular, FOCUS-MUSE DWI showed superior performance on susceptibility artifacts, geometric distortion, anatomical details, and overall image quality, yet a lower SNR, compared to FOCUS DWI.

FOCUS-MUSE DWI is an integration imaging sequence with features of less interference from surrounding tissues, geometric distortion, field susceptibility, and motion artifacts, resulting in superior subjective assessment at geometric distortion, lesion conspicuity, and anatomical details on syFOCUS-MUSEb =1,500 to syFOCUSb =1,500. Previously, FOCUS DWI had been shown to improve delineation for mucosal infiltration of cervical cancer (16), indicating that anatomical details played an important role in assessing the infiltration of CC in the parauterine organ. A study of pancreatic cancer has reported the superior subjective assessment and inter-observer ADC measurements using FOCUS-MUSE DWI compared to MUSE DWI and FOCUS DWI, yet inferior SNR, of FOCUS-MUSE DWI compared to MUSE DWI (7). Computed DWIs with a b-value of 1,400 s/mm2 have provided better lesion differentiation for biliary malignancies than sDWIs with a b-value of 800 s/mm2 (28); consistently, syFOCUS-MUSEb =1,500 with the best inter-reader consistency of susceptibility artifacts and anatomical details may elevate subjective diagnosis of CC stage. Additionally, sFOCUS-MUSEb =800 and syFOCUS-MUSEb =1,500 respectively showed lower SNR than sFOCUSb =800 and syFOCUSb =1,500, likely attributing to the longer minimum TE of FOCUS-MUSE DWI than FOCUS DWI (88.5 vs. 80.7 ms). However, SNR of FOCUS-MUSE DWI (28.05) with high spatial resolution was sufficient to be utilized compared to the reported SNR of FOCUS DWI (27.79) (5).

ADC value is used to evaluate tissue diffusion characteristics and is considered an effective tool to predict the histological subtypes, tumor grade, and treatment response of cervical cancer (29). ADC is affected by factors such as gradient intensity, diffusion time, and image intensity (30,31). Nevertheless, FOCUS-MUSE DWI and FOCUS DWI have showed no statistical difference between patient and healthy groups, possibly for both shared features such as reduced FOV, minimal geometric distortion, better anatomical clarity, and similar CNR. Previous studies have shown no significant ADC difference in female pelvis (32) and prostate (33) tissues between FOCUS DWI and MUSE DWI, but significantly lower ADC value in the non-cancer prostate region using FOCUS DWI than MUSE DWI. This indicates that FOV does not significantly affect ADC values. Moreover, susceptibility distortion correction can improve the accuracy of ADC quantification. Our finding of lower ADC values in each group using FOCUS-MUSE DWI than FOCUS DWI may be attributed to the TE difference between two sequences. Similarly, FOCUS-MUSE DWI-computed ADC maps have shown non-insignificantly lower ADC values than FOCUS DWI-generated maps in lung disease (13). However, the analysis of all participants revealed significantly lower ADC values for FOCUS-MUSE DWI vs. FOCUS DWI. This difference may arise from variations in TE settings, reflecting the correlation between the application of diffusion gradients and longer TE during data acquisition (34). Additionally, when tissue T2 varies, its correlation with ADC values differs: T2 negatively correlates with ADC at shorter T2 times (<70 ms) but positively correlates in longer T2 regimes (>70 ms) (35,36). Therefore, TE settings in diffusion images significantly influence diffusion signal changes. When using ADC values to assess cellularity, careful attention to diffusion TE settings is essential. In the future, slow diffusion coefficient (SDC), a novel MRI diffusion metric, may assist clinical diagnosis, as SDC is not dominant by T2 effects, and may reflect the true diffusion characteristics in tissue microstructures (36).

The first edition of the National Comprehensive Cancer Network (NCCN) Cervical Cancer Clinical Practice in 2020 (37) pointed out that surgical treatment is not recommended for patients with FIGO stage IIB and above, and that selective treatments are recommended for those below stage IIB based on the depth and diameter of tumor invasion and presence of lymphatic metastasis and vascular infiltration. The clinical diagnosis and assessment and risk prediction of patients before surgery contribute to appropriate treatment plans since recurrence and metastasis of early cervical cancer possibly occur after surgery. A negative correlation between mean ADC values and cervical cancer stages assists preoperative and postoperative evaluation of cervical cancer, especially postoperative supplementary therapy with a threshold for ADC mean of less than 0.910×10−3 mm2/s (38). In terms of body tissues, ADC values using DWIs with b-values of 0 and <200 s/mm2 as well as >1,000 s/mm2 respectively reflect intracellular (slow) and extracellular (fast) diffusion rate of water molecules in corresponding to the cellular density (e.g., concentration of water-bound macromolecules and cell size) and complexity of tissue microstructure (39). That is, ADC values can classify histological subtypes of CC, tumor grade, and treatment responses based on diffusion displacement of water molecules within a voxel (29). In addition, voxel-by-voxel histogram analysis of DWIs with different b-values further elevate differentiation of molecule status in glioma (40) [isocitrate dehydrogenase (IDH), cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B), epidermal growth factor receptor (EGFR)] as well as offer diagnosis and prognosis of tumor histological heterogeneity information. Consistently, our results showed that sADC and syADC were lower in patients with late-stage cervical cancers than they were in patients with early-stage cervical cancers and healthy controls. Additionally, the diagnostic efficiency for FOCUS-MUSE-syADCb =1,500 was identical to those of FOCUS-MUSE-sADCb =800, FOCUS-syADCb =1,500, and FOCUS-syADCb =1,500. Similarly, there was the excellent agreement on diagnostic performance for syADCb =1,500 in the assessment of liver, spleen, and paravertebral muscles in pediatric patients (27). In other words, high-b-value-computed ADC could be derived from low-b-value DWIs with relatively small errors regardless of magnetic field strength (26,41). syFOCUS-MUSEb =1,500 with both features of MUSE DWI and FOCUS DWI mitigated imaging interference factors and had more reliable ADC values for tumor staging.

Our study had some limitations. Firstly, all data were collected at a single center. Insufficient samples for each subcategory corresponding to its pathological type and histological grade restricted between-subcategory comparisons, leading to biased and limiting generalization. Secondly, synthetic FOCUS-MUSE DWI and FOCUS DWI with b =1,500 mm/s2 were extrapolated using a five b-value scheme, rather than interpolated, based on our previous finding that syFOCUS DWI with b =1,500 mm/s2 demonstrated superior clinical value to both synthetic and actually-scanned FOCUS DWI with b =1,200 mm/s2 on 1.5 T. Given that synthetic DWIs with a b-value of 1,500–2,000 mm/s2 optimizes prostate cancer detection, future work will expand the sample size and sketch entire lesions to compare the sensitivity of different DWI sequences across b-values for distinct stages of cervical cancer. Thirdly, ADC measurements were drawn solely on the maximum tumor cross-section which may not capture overall heterogeneity. Finally. high T2 dependence limits ADC’s reliability as a standalone biomarker for true diffusivity—although it partially reflects diffusion properties, it remains substantially confounded by relaxation effects. Notably, when tissue T2 approaches 70 ms (the intermediate regime), ADC values may exhibit paradoxical reductions due to competing T2 influences. Therefore, protocol-specific TE settings must be accounted for when using ADC for cellular differentiation assessment. Future implementations should incorporate SDC calculations to supplement diagnosis and mitigate T2 confounding.

Conclusions

Compared to both synthetic and scanned FOCUS DWI as well as scanned FOCUS-MUSE DWI, syFOCUS-MUSEb =1,500 showed superior overall image quality and lesion details, and the corresponding ADC values had equivalent efficacy of ADC in distinguishing patients, especially those with early-stage cervical cancer from normal controls and patients with late-stage cervical cancer on 3.0 T MRI. Our study suggested that synthetic high-b-value FOCUS MUSE DWI with synthetic high-b-value DWIs would benefit patients with cervical cancer in the aspect of no additional scan time as well as a radiologist’s diagnostic confidence.

Acknowledgments

We thank the individuals with cervical cancer and the healthy controls for participating in this study.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-338/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-338/dss

Funding: This work was supported by the Natural Science Foundation of Hubei Province (grant No. 2023AFC033).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-338/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and approved by the Ethics Review Committee of Taihe Hospital, Shiyan City (IRB No. 2024KS11). All participants in the study have provided written informed consent.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: Mei W, Li C, Tang Q, Sang L, Wang S, Zhou Q, Xu L, Liu WV, Chen W. Prospective comparison of synthetic high b-value field of view optimized and constrained undistorted multiplexed sensitivity encoding (FOCUS-MUSE) and FOCUS diffusion-weighted imaging in evaluating cervical cancer. Quant Imaging Med Surg 2025;15(10):10006-10019. doi: 10.21037/qims-2025-338

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