{"paper_id":"6e586c99-f1be-4325-bdc5-4305829d7def","body_text":"International Journal of Hyperthermia\nISSN: 0265-6736 (Print) 1464-5157 (Online) Journal homepage: www.tandfonline.com/journals/ihyt20\nNon-contrast enhanced MRI for efficiency\nevaluation of high-intensity focused ultrasound in\nadenomyosis ablation\nMa Si, Fajin Lv, Mingmei Tang, Yang Liu, Xueke Qiu, Chunmei Gong, Yan Hu &\nYang Liu\nTo cite this article: Ma Si, Fajin Lv, Mingmei Tang, Yang Liu, Xueke Qiu, Chunmei Gong, Yan\nHu & Yang Liu (2024) Non-contrast enhanced MRI for efficiency evaluation of high-intensity\nfocused ultrasound in adenomyosis ablation, International Journal of Hyperthermia, 41:1,\n2295813, DOI: 10.1080/02656736.2023.2295813\nTo link to this article:  https://doi.org/10.1080/02656736.2023.2295813\n© 2024 The Author(s). Published with\nlicense by Taylor & Francis Group, LLC\nPublished online: 17 Jan 2024.\nSubmit your article to this journal \nArticle views: 1194\nView related articles \nView Crossmark data\nCiting articles: 2 View citing articles \nFull Terms & Conditions of access and use can be found at\nhttps://www.tandfonline.com/action/journalInformation?journalCode=ihyt20\n\nNon-contrast enhanced MRI for efficiency evaluation of high-intensity focused \nultrasound in adenomyosis ablation\nMa Si\na ,b\n, Fajin Lv\na,b ,c ,d\n, Mingmei Tang\na\n, Yang Liu\na ,b\n, Xueke Qiu\na ,b\n, Chunmei Gong\na ,b\n, Yan Hu\na ,b \nand Yang Liu\na ,b,c \na\nState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, \nChongqing, China; \nb\nChongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, China; \nc\nDepartment \nof Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; \nd\nInstitute of Medical Data, Chongqing \nMedical University, Chongqing, China \nABSTRACT \nObjective: To investigate the value of T2-weighted imaging (T2WI) and diffusion-weighted imaging \n(DWI) in evaluating the therapeutic effect of high-intensity focused ultrasound (HIFU) in adenomyosis \nablation.\nMaterial and methods: One hundred eighty-nine patients with adenomyosis were treated with HIFU. \nThe ablation areas on T2WI and DWI sequences were classified into different types: type I, relatively ill- \ndefined rim or unrecognizable; subtype IIa, well-defined rim with hyperintensity; subtype IIb, well- \ndefined rim with hypointensity. The volume of ablation areas on T2WI (V\nT2WI\n) and DWI (V\nDWI\n) was \nmeasured and compared with the non-perfused volume (NPV), and linear regression was conducted \nto analyze their correlation with NPV.\nResults: The V\nT2WI \nof type I and type II (subtype IIa and subtype IIb) were statistically different from \nthe corresponding NPV (p ¼ 0.004 and 0.024, respectively), while no significant difference was found \nbetween the V\nDWI \nof type I and type II with NPV (p ¼ 0.478 and 0.561, respectively). In the linear \nregression analysis, both V\nT2WI \nand V\nDWI \nwere positively correlated with NPV, with R\n2 \nreaching 0.96 \nand 0.97, respectively.\nConclusions: Both T2WI and DWI have the potential for efficient evaluation of HIFU treatment in \nadenomyosis, and DWI can be a replacement for CE-T1WI to some extent.\nAbbreviations: HIFU: high-intensity focused ultrasound ; NPV: non-perfused volume ; NPVR: non-per -\nfused volume ratio ; V\nT2WI\n: ablation volume on T2WI ; V\nDWI\n: ablation volume on DWI ; ICC: intraclass cor -\nrelation coefficient ; MRI: magnetic resonance image ; T2WI: T2-weighted imaging ; DWI: diffusion- \nweighted imaging ; CE-T1WI: contrast-enhanced T1WI ; BMI: body mass index ; IT: interval time between \nHIFU procedure and MRI scanning post-treatment ; EEF: energy efficiency factor\nARTICLE HISTORY \nReceived 13 June 2023 \nRevised 11 December 2023 \nAccepted 12 December 2023 \nKEYWORDS \nHigh-intensity focused \nultrasound; magnetic \nresonance imaging; \nadenomyosis; non-perfused \nvolume; efficiency \nevaluation   \nIntroduction\nAdenomyosis is a common and benign uterine disease that \naffects women during their childbearing age. Its typical \npathological findings are ectopic endometrial glands, stromal \ntissue in the myometrium, and hyperplasia of the peripheral \nsmooth muscle [ 1 ]. Adenomyosis can seriously impair the \nquality of life. About 2/3 of patients have symptoms of dys -\nmenorrhea or menorrhea and some patients may experience \ninfertility [ 2 , 3 ]. In addition to medication and surgery, high- \nintensity focused ultrasound (HIFU) ablation is a novel \nmethod for adenomyosis treatment. By focusing ultrasonic \nenergy on the target tissue, HIFU treatment can cause \ncoagulative necrosis and reduce the volume of the lesion [ 4 ]. \nHIFU treatment contains the advantage of being highly effi -\ncient, noninvasive, and inexpensive [ 5 , 6 ].\nTo estimate the prognosis of the patients, the evaluation \nof treatment efficacy is necessary. MRI is one of the most \nimportant methods for efficacy evaluation post-treatment. \nThe ablation rate, represented by the non-perfused volume \nratio (NPVR), is the most widely used index for evaluating \nthe short-term efficacy of HIFU. NPVR is defined as the ratio \nof the non-perfused volume (NPV) measured on post-treat -\nment contrast-enhanced T1-weighted imaging (CE-T1WI) to \nthe adenomyosis volume measured on pretreatment T2- \nweighted imaging (T2WI). It has been confirmed that NPVR \nhas a significant positive correlation with the prognosis of \nthe patients. Therefore, the NPVR has been the gold standard \nin the efficacy evaluation of HIFU treatment [ 7–9 ]. However, \nthe use of gadolinium-based contrast agents in CE-T1WI may \nincrease money consumption and time costs. Furthermore, it \nCONTACT Yang Liu \n 249572846@qq.com \n State Key Laboratory of Ultrasound Engineering in Medicine and Engineering, College of Biomedical \nEngineering, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing, 400016, China; Chongqing Key Laboratory of Biomedical Engineering, \nChongqing Medical University, Chongqing, China; Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China \nSi Ma and Fajin Lv are both first authors. \n� 2024 The Author(s). Published with license by Taylor & Francis Group, LLC \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, \ndistribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted \nManuscript in a repository by the author(s) or with their consent.\nINTERNATIONAL JOURNAL OF HYPERTHERMIA \n2024, VOL. 41, NO. 1, 2295813 \nhttps://doi.org/10.1080/02656736.2023.2295813\n\nmay also pose potential risks to patient health, such as neph -\nrogenic systemic fibrosis (NSF), contrast-induced nephrop -\nathy, and anaphylaxis [ 10–12 ]. An MRI method that can \nquickly and effectively evaluate the efficacy of HIFU in \nadenomyosis treatment without the use of contrast agents \nmay significantly improve its economy and safety.\nT2-weighted imaging (T2WI) and diffusion-weighted imag -\ning (DWI) are MR sequences with fast imaging and without \ncontrast agent use. Several studies have reported their value \nin the efficiency evaluation of HIFU treatment in leiomyomas \n[ 13–15 ]. The signal change of micro hemorrhage on T2WI \ncan make the boundary between ablation areas and fibroid \ntissue. Furthermore, Liao DF’s study found that a high-signal \nring on DWI after HIFU ablation could help to measure the \narea of necrotic tissue and evaluate the success of the pro -\ncedure. However, their value in efficiency evaluation for HIFU \ntreatment in adenomyosis remains unknown.\nMaterial and methods\nPatients\nPatients with symptomatic adenomyosis who underwent \nHIFU treatment (between June 2013 and September 2019) \nwere enrolled in this study ( Figure 1 ). The inclusion criteria \nwere as follows: (1) Adult women with symptomatic \nadenomyosis; (2) the patients should be completely \nautonomous and cooperate to complete HIFU treatment; \nand (3) the patients should undergo pelvic MRI scanning \nbefore and after HIFU treatment. The exclusion criteria \nwere as follows: (1) age < 18 years, (2) inability to com -\nplete the treatment, (3) lack of clinical or imaging data, (4) \nother pelvic malignancies, and (5) acute pelvic inflamma -\ntion and pregnancy.\nHIFU treatment\nThe patient ingested liquid food three days before treatment \nand a single dose of intestinal preparation solution (2000 ml \nof composite polyethylene glycol electrolyte solution) in the \nafternoon before treatment. An enema was performed on \nthe morning of the day of treatment. The treated area was \nshaved, degreased, and degassed in advance. The patient \nwas prone on the operating table, and the anterior abdom -\ninal wall was in contact with degassed water. A catheter was \ninserted to control bladder volume by injecting saline, and a \ndegassed water balloon was used to push away the intestine \nin the acoustic path.\nThe HIFU procedure was performed using a Focused \nUltrasound Tumor Therapeutic System (Model-JC or Model-JC \n200, Chongqing Haifu Medical Technology Co., Ltd.). The \nultrasound parameters used in this study were as follows: a \nworking frequency of 0.8 MHz, an acoustic power range of \n300–400 W, and a focal area of 1.5 mm � 1.5 mm � 10 mm. \nThe ultrasound device provided real-time monitoring during \nthe HIFU procedure. The patient was treated under intraven -\nous conscious sedation with fentanyl and midazolam hydro -\nchloride. The ultrasonic energy was adjusted based on both \npatient’s feedback and changes in gray scale on ultrasono -\ngraphic imaging during the treatment. The physician discon -\ntinued the treatment until the grayscale covered most of the \nlesion or the patient could not endure the pain of the pro -\ncedure. When the treatment ended, the patient was asked to \nobserve for 2 h before they returned to the ward.\nMRI evaluation\nAll patients were scanned with 3.0 T MRI equipment (single \nHD excite, GE Healthcare, USA) before and after HIFU treat -\nment. The eight-channel phased-array abdominal coil was \nFigure 1. The recruitment process of patients in this study.\n2\n M. SI ET AL.\n\nfixed in a supine position. Patients were asked to breathe \ncalmly and avoid body movements during the examination. \nThe scanning parameters are presented in Table 1 .\nThe types of ablation areas, non-perfused volume (NPV), \nthe ablation volume on T2WI (V\nT2WI\n), the ablation volume \non DWI (V\nDWI\n), and the volume of adenomyosis were \nevaluated.\nThe types of ablation areas were classified independently \nby radiologists 1 and 2 (both with eight years of experience \nin MRI diagnosis). In cases of disagreement in classification \nbetween the two radiologists, the final decisions were made \nby radiologist 3 (10 years of experience in MRI diagnosis). All \nthree radiologists were blinded to the patient’s information \nand post-treatment CE-T1WI images. The ablation areas on \nT2WI and DWI were respectively classified according to the \nfollowing criteria ( Figure 2 ): (1) type I, the ablation area had \na relatively ill-defined rim which was either hyperintensity or \nhypointensity or unrecognizable; (2) subtype IIa, the ablation \narea had a well-defined rim which was hyperintensity; (3) \nand subtype IIb, the ablation area had a well-defined periph -\neral rim which was hypointensity. When evaluating the abla -\ntion areas, the central slice that could manifest the largest \npart of the ablation area was used and pretreatment images \nwere selected as a reference. The consistency of the classifi -\ncation of the ablation areas between the two radiologists \nwas evaluated using the kappa consistency test.\nThe ablation volume on T2WI (V\nT2WI\n), the ablation volume \non DWI (V\nDWI\n), and NPV were measured on post-treatment \nT2WI, DWI (b ¼ 800 m\n2\n/s) and CE-T1WI. Adenomyosis volume \nwas measured on pretreatment T2WI. The volumes were \nmeasured by delineating all the slices of the target areas \nusing the ITK-SNAP 3.4 software (Cognitica, Philadelphia, PA, \nUSA) and the volumes were calculated automatically ( Figure \n3 ). When measuring the type I ablation volumes, the regions \nwith suspicious signal change at the rim should all be cov -\nered. For patients whose ablation areas were unrecognized, \nwe defined the V\nT2WI \nor V\nDWI \nas 0 cm\n3\n. V\nT2WI \nand V\nDWI \nwere \ncompared to the corresponding NPV. Linear regression ana -\nlysis was performed to assess their correlations.\nBased on their ablation types on T2WI, the patients \nwere divided into the T2WI-type I group and the T2WI- \ntype II group, the T2WI-type II group was then divided \ninto T2WI-subtype IIa group and T2WI-subtype IIb group. \nThe patients were also classified into DWI-type I group, \nDWI-type II group, DWI-subtype IIa group, and DWI-subtype \nIIb group according to their ablation types on DWI. The \nclinical and treatment parameters were compared between \nthe groups.\nStatistical analysis\nAll analyses were performed using the SPSS software (SPSS \n24.0 IBM Company, Armonk, NY, USA). Normally distributed \ndata were reported as mean ± standard deviation, whereas \nnon-normally distributed data were reported as medians and \ninterquartile ranges. The t-test or rank sum test was used to \ncompare differences in measurement data, and the chi- \nsquare test was used to compare differences in counting \ndata. The interpretation of the Kappa value is based on the \nfollowing criteria: a Kappa value < 0.2 indicates poor consist -\nency; a Kappa value between 0.21 and 0.40 indicates fairly \npoor consistency; a Kappa value between 0.41 and 0.60 indi -\ncates moderate consistency; a Kappa value between 0.61 \nand 0.80 indicated fairly good consistency; and a Kappa \nvalue > 0.80 indicates good consistency. An intraclass correl -\nation coefficient above 0.90 was classified as having good \nreliability. Statistical significance was set at p < 0.05.\nResults\nGeneral characteristic\nIn total, 189 patients were enrolled in this study. The mean age \nwas 41 ± 5 years, and the mean BMI was 32.1 ± 2.9. The median \nadenomyosis volume was 94.4 (53.5–196.2) cm\n3\n. The median \nNPV was 43.2 (23.7–78.8) cm\n3 \nand the median NPVR was 44.1 \n(30.9–62.3) %. The interval time between the HIFU procedure \nand post-treatment MRI scanning (IT) was 1 (1–3) days and 141 \npatients underwent MRI examination within 2 days.\nThe classification of ablation areas on T2WI and DWI\nOf the 189 adenomyosis on T2WI, 31 of them presented type I \nablation areas, 119 of them presented subtype IIa ablation areas \nand 39 of them presented subtype IIb ablation areas. In all 189 \nablation areas on DWI, 15 of them were type I ablation areas, \n121 of them were subtype IIa ablation areas, and 53 of them \nwere subtype IIb ablation areas. The kappa value of the classifi -\ncation for the ablation area on T2WI was 0.627 (p < 0.001) \nbetween the two radiologists, and that on DWI was 0.651 \n(p < 0.001). Both reached fairly good consistency ( Table 2 ).\nThe measurement of ablation volume on T2WI and DWI\nThe median V\nT2WI \nof type I and type II ablation area were \n15.0 (5.3–33.5) cm\n3 \nand 50.4 (23.2–114.8) cm\n3\n, both of which \nwere significantly different (p ¼ 0.004 and p ¼ 0.024, \nTable 1. MRI parameters.\nTR (ms) TE (ms) NEX FOV (cm � cm) Matrix size Slice thickness (mm) Slice gap (mm) Imaging planes\nT2WI (FSE) 4080 105 2 38 � 47.2 512 � 512 6 2 Transverse \nSagittal\nT1WI (SE) 600 10 1 38 � 47.2 512 � 512 6 2 Transverse\nDWI (SE-EPI) \n(b ¼ 0, 800 m\n2\n/s)\n5700 65.7 2 38 � 38 256 � 256 5 0 Transverse\nCE-MRI (LAVA) 4.2 1.9 0.72 38 � 38 512 � 512 4 0 Transverse \nSagittal\nT2WI: T2-weighted imaging; T1WI: T1-weighted imaging; DWI: diffusion-weighted imaging; CE-MRI: contrast-enhanced MRI; TR: repetition time; TE: echo time; \nFOV: field of view; NEX: number of excitations.\nINTERNATIONAL JOURNAL OF HYPERTHERMIA\n 3\n\nrespectively) with their corresponding NPV, which were 21.2 \n(8.7–42.8) cm\n3 \nand 49.1 (27.9–94.9) cm\n3\n, respectively. And \nthe V\nDWI \nof type I and type II ablation area were 9.4 (3.7– \n24.6) cm\n3 \nand 57.1 (33.5–122.3) cm\n3\n, both of which with no \nsignificant difference (p ¼ 0.078 and p ¼ 0.561) with their cor -\nresponding NPV, which were 13.9 (6.3–26.6) cm\n3 \nand 58.8 \n(30.1–118.4) cm\n3\n. Seven patients got invisible ablation areas \non T2WI, their largest NPV and NPVR were 18.5 cm\n3 \nand \n17.7% and their smallest NPV and NPVR were 2.2 cm\n3 \nand \n2.0%. Five patients had completely invisible ablation areas \non DWI, their largest NPV and NPVR were 6.3 cm\n3 \nand 13.8% \nand their smallest NPV and NPVR were 2.2 cm\n3 \nand 2.0%. \nThe ICC of the measurement for V\nT2WI \nwas 0.951 in the type \nI group and that was 0.990 in type II group. The ICC of the \nmeasurement for V\nDWI \nwas 0.947 in type I group and that \nwas 0.975 in type II group. All achieved good consistency \n( Table 3 ).\nIn the linear regression analysis, both V\nT2WI \nand V\nDWI \nshowed significant correlations with the NPV. The linear \nequation between V\nT2WI \nand NPV was NPV ¼ 0.98 V\nT2WI \nþ\n1.32 (R\n2 \n¼ 0.96, p < 0.001). The linear equation between V\nDWI \nand NPV was NPV ¼ 0.96 V\nT2WI \nþ 1.07 (R\n2 \n¼ 0.97, p < 0.001) \n( Figure 4 ).\nClinical and treatment parameters of the different \ngroups\nThe age, BMI, adenomyosis volume, adenomyosis type, ute -\nrus position, NPV, sonication power, treatment time, \nsonication time, sonication dose, energy efficiency factor \n(EEF, defined as the ultrasound energy delivered for ablating \n1 mm\n3 \nof the adenomyotic lesion tissue), NPVR, and IT of the \ndifferent groups were compared. The NPV in the T2WI-type I \ngroup was 21.2 (8.7–42.8) cm\n3\n, while the NPV was 49.1 \n(27.9–94.9) cm\n3 \nin the T2WI-type II group (p < 0.01). The \nNPVR in the T2WI-type I group was 27.2 (17.4–44.7)%, while \nthat was 54.6 (42.0–73.9)% in the T2WI-type II group \n(p < 0.01). The NPV in the DWI-type I group was 13.9 (6.3– \n26.6) cm\n3\n, and that was 58.8 (30.1–118.4) cm\n3 \nin the DWI- \ntype II group (p < 0.01). The same difference was found \nbetween the NPVR in the DWI-type I and DWI-type II group \n(32.5 (13.4–48.5)% vs. 43.0 (30.0–68.7)%, p < 0.001). The EEF \nin the DWI-type I group was 4.1 (2.5–6.8) kJ/cm\n3\n, and the \nEEF in the DWI-type II group was 2.0 (1.4–4.3) kJ/cm\n3 \n(p ¼ 0.044). And the volume of adenomyosis in the DWI-type \nI group was smaller than that in the DWI-type II group (68.7 \n(33.6–93.9) cm\n3 \nvs. 148.2 (76.3–266.1) cm\n3\n, p ¼ 0.001). The \nresults are shown in Tables 4 and 5 .\nA remarkable statistical significance was found between \nthe ITs in the T2WI-subtype IIa and T2WI-subtype IIb groups \n(1 (1–2) days vs. 5 (2–7) days, p < 0.001), and the same differ -\nence was also found between the DWI-subtype IIa and IIb \ngroups (1 (1–3) days vs. 6 (3-6) days, p < 0.001). The EEF and \nsonication time [2.4 (1.5–7.8) kJ/cm\n3 \nand 597 (397–1213) s] in \nthe T2WI-subtype IIa group were smaller than those [2.9 \n(1.9–4.6) kJ/cm\n3 \nand 912 (489–1200) s] in the T2WI-subtype \nIIb group. The treatment time in the T2WI-subtype IIa group \nwas 52 (35–93) min, which was smaller than the treatment \nFigure 2. T2WI (A1, B1, C1), DWI (A2, B2, C2), and CE-T2WI (A3, B3, C3) images post-treatment. As we can see, the subtype IIa and IIb ablation areas on T2WI or \nDWI had similar morphology with corresponding non-perfused area on CE-T1WI (B3 and C3).\n4\n M. SI ET AL.\n\ntime of 88 (61–102) min in the T2WI-subtype IIb group. And \nthe NPV and NPVR in the DWI-subtype IIb group were larger \nthan those in the DWI-subtype IIa group [54.6 (19.3–83.2) \ncm\n3 \nvs. 52.6 (21–113.5) cm\n3\n, p ¼ 0.026 and 67.7 (35.2–79.5)% \nvs 44.1 (35.8–68.5)%, p ¼ 0.013). Furthermore, the sonication \npower was slightly higher in the DWI-subtype IIa group (400 \n(373-400) W vs. 398 (371–400) W, p ¼ 0.013). The results are \nshown in Tables 6 and 7 .\nDiscussion\nThe ultrasound energy in HIFU ablation leads to an interrup -\ntion of blood flow in the ablation tissue. As a result, the \ntreated tissue appears as the non-perfused area on CE-T1WI \n[ 16 ]. At present, the NPVR has become the gold standard for \nefficient evaluation of HIFU treatment since it has a positive \ncorrelation with the patient’s prognosis [ 7–9 ]. However, the \nuse of gadolinium-based contrast agents is time- and \nmoney-consuming and may pose potential risks. Therefore, it \nis more economical and safer to use the non-contrast MRI \ntechnique for efficacy evaluation. In leiomyomas, the value \nof T2WI and DWI in the efficacy evaluation of HIFU treatment \nhas been revealed [ 13–15 ]. However, their potential for eval -\nuating HIFU treatment in adenomyosis remains unknown.\nAccording to the image features of the ablation area on \nT2WI or DWI, they were classified into type I (with an ill- \ndefined rim) and type II (with a well-defined rim). The main \ndifferences in treatment parameters between the type I \ngroup and the type II group were their NPV and NPVR. \nAdenomyosis patients with type I ablation areas on T2WI or \nFigure 3. The measurement of V\nT2WI\n, V\nDWI, \nNPV and volume of adenomyosis. A. Measurement of volume of adenomyosis on pretreatment T2WI; B. Measurement \nof V\nT2WI \non post-treatment T2WI; C. Measurement of V\nDWI \non post-treatment DWI; D. Measurement of NPV on post-treatment CE-T1WI.\nTable 2. Inter-reader agreement in classifying ablation types on T2WI \nand DWI.\nT2WI types Radiologist2\nKappa pRadiologist1 Type I Subtype IIa Subtype IIb\nType I 21 1 3\nSubtype IIa 6 94 22\nSubtype IIb 3 5 34\n0.627 0.000 \nDWI types Radiologist2\nKappa PRadiologist1 Type I Subtype IIa Subtype IIb\nType I 9 1 3\nSubtype IIa 5 102 16\nSubtype IIb 0 9 44\n0.651 0.000\nTable 3. Inter-reader agreement in measuring V\nT2WI \nand V\nDWI\n.\nRadiologist 1 Radiologist 2 ICC P\nV\nT2WI \nof type I (cm\n3\n) 15.0 (5.3–33.5) 13.9 (4.6–38.0) 0.951 0.000\nV\nT2WI \nof type II (cm\n3\n) 50.4 (23.2–114.8) 53.2 (26.1–124.4) 0.958 0.000\nV\nDWI \nof type I (cm\n3\n) 9.4 (3.7–24.6) 7.1 (3.0–24.2) 0.947 0.000\nV\nDWI \nof type II (cm\n3\n) 57.1 (33.5–122.3) 55.9 (34.2–123.8) 0.975 0.000\nINTERNATIONAL JOURNAL OF HYPERTHERMIA\n 5\n\nDWI were associated with lower NPV and NPVR, indicating \nthat a type I ablation area on T2WI or DWI may suggest rela -\ntively poor treatment efficiency. Previous studies have also \nfound that lesion volume and EEF are related to NPVR [ 17 , \n18 ], which may explain why EEF and lesion volume were also \ndifferent between type I and type II.\nFigure 4. Linear correspondence between V\nT2WI \nand NPV and V\nDWI \nand NPV. A. The scatter diagram of correspondence betweenV\nT2WI \nand NPV; B. The scatter dia -\ngram of correspondence between V\nDWI \nand NPV.\nTable 4. Comparison of clinical and treatment parameters between T2WI-type I and T2WI- type II group.\nAblation types on T2WI\npType I Type II\nAge 39 ± 5 41 ± 5 0.081\nBMI 23.1 ± 2.4 23.1 ± 2.9 0.987\nAdenomyosis volume (cm\n3\n) 80.7 (45.6–112.7) 109.9 (51.2–225.7) 0.084\nTypes of adenomyosis (diffuse/focus) 22/9 126/32 0.340\nPosition involved in uterus\nAnterior (yes/no) 18/13 76/82 0.310\nPosterior (yes/no) 21/10 105/53 0.890\nFundus (yes/no) 8/23 56/102 0.310\nNPV (cm\n3\n) 21.2 (8.7–42.8) 49.1 (27.9–94.9) 0.000\n�\nSonication power (W) 400 (366–400) 400 (373–400) 0.400\ntreatment time (min) 80.7 ± 29.5 78.8 ± 51.9 (40.8–94.3) 0.535\nSonication time (s) 840.2 ± 373.3 882.4 ± 581.0 0.754\nSonication dose (kJ) 309.9 ± 159.3 343.4 ± 229.3 0.446\nEEF (kJ/cm\n3\n) 4.0 (2.5-5.5) 2.8 (1.4–4.7) 0.061\nNPVR (%) 27.2 (17.4–44.7) 54.6 (42.0–73.9) 0.000\n�\nIT (d) 2.0 (1.0–3.0) 2.5 (1.0–6.0) 0.238\nT2WI: T2-weighted imaging; T1WI: T1-weighted imaging; DWI: diffusion-weighted imaging; CE-MRI: contrast-enhanced MRI; TR: repetition \ntime; TE: echo time; FOV: field of view; NEX: number of excitations.\nTable 5. Comparison of clinical and treatment parameters between DWI-type I and DWI-type II group.\nAblation types on DWI\nPType I Type II\nAge 40 ± 6 41 ± 6 0.628\nBMI 23.7 ± 2.5 23.1 ± 2.9 0.444\nAdenomyosis volume (cm\n3\n) 68.7 (33.6–93.9) 148.2 (76.3-266.1) 0.001\n�\nTypes of adenomyosis (diffuse/focus) 10/5 138/36 0.254\nPosition involved in uterus\nAnterior (yes/no) 7/8 87/87 0.804\nPosterior (yes/no) 11/4 115/59 0.568\nFundus (yes/no) 1/14 63/111 0.020\nNPV (cm\n3\n) 13.9 (6.3–26.6) 58.8 (30.1–118.4) 0.000\n�\nSonication power (W) 400 (359–400) 400 (390–400) 0.458\ntreatment time (min) 70.2 ± 32.1 79.8 ± 49.9 0.481\nSonication time (s) 785.3 ± 349.2 882.7 ± 564.9 0.526\nSonication dose (kJ) 272.3 ± 151.4 343.3 ± 23.6 0.245\nEEF (kJ/cm\n3\n) 4.1 (2.5–6.8) 2.0 (1.4–4.3) 0.044\n�\nNPVR (%) 32.5 (13.4–48.5) 43.0 (30.0–68.7) 0.006\n�\nIT (d) 1.0 (1.0–1.3) 2.5 (1.0–5.3) 0.105\nBMI: body mass index; EEF: energy efficiency factor; IT: interval time between HIFU procedure and MRI scanning post-treatment.\n6\n M. SI ET AL.\n\nThe type II ablation areas on T2WI and DWI were further \nclassified into subtypes IIa and IIb on the basis of the signal \nintensity of their rims. Sixty-three percent (119/189) of the \nablation areas on T2WI belonged to subtype IIa, while 64.0% \n(121/189) of the ablation areas on DWI belonged to subtype \nIIa. Each of them had a core of heterogeneous signal inten -\nsity and a rim of hyperintensity that delineated the edge of \nthe ablation area. This distinctive appearance may be due to \nthe difference in energy distribution in the ablation area [ 19 , \n20 ]. The central part absorbed more ultrasonic energy and \nresulted in coagulative necrosis, while the peripheral part \nabsorbed less ultrasonic energy. Its pathological change was \ncytotoxic edema, which presented high intensity on T2WI \nand DWI. This phenomenon was also observed in previous \nstudies [ 21 , 22 ].\nThe remaining ablation areas on T2WI and DWI were clas -\nsified as subtype IIb, and they had apparent rims of hypoin -\ntensity. It is noteworthy that the median IT of patients with \nsubtype IIb ablation areas on T2WI and DWI was longer. The \nIT of some patients in our study exceeded 2 days. Generally, \nMRI scans within 2 days after the HIFU treatment would \nallow physicians to better understand the success of the pro -\ncedure. We still enrolled these patients in our study because \nwe found the IT may somehow impact the image features of \nthe ablation area on T2WI and DWI. When the IT was long \nenough, the local micro-hemorrhage would gradually trans -\nform into paramagnetic material, such as deoxyhemoglobin \nor methemoglobin, which could appear as low signal inten -\nsity on T2WI and DWI [ 23 , 24 ]. In the meantime, the local \ncytotoxic edema also faded over time [ 21 ]. The MR findings \nof subtype IIb on T2WI and DWI were not observed in previ -\nous reports [ 13 , 25 , 26 ]. This difference might be caused by \nthe different objects and IT in various studies. The EEF, treat -\nment time, and sonication time between the T2WI-subtype \nIIa group and the T2WI-subtype IIb group showed statistical \ndifferences. While, the NPVR, NPV, and sonication power \nbetween the DWI-subtype IIa group and the DWI-subtype IIb \ngroup also showed statistical differences. The results above \nshowed that the HIFU parameters and treatment difficulty of \nadenomyosis may affect the appearance of lesions on T2WI \nand DWI to some extent. However, the specific mechanism \nremained unclear.\nBoth V\nT2WI \nand V\nDWI \npresented high correlations with NPV, \nwhich may imply that T2WI and DWI have the potential to \nbe optional methods for evaluating the efficiency of HIFU \ntreatment for adenomyosis. The V\nT2WI \nof types I and II were \nTable 6. Comparison of clinical and treatment parameters between T2WI-subtype IIa and T2WI-subtype IIb group.\nAblation subtypes on T2WI\npSubtype IIa Subtype IIb\nAge 41 ± 6 40 ± 5 0.118\nBMI 23.1 ± 2.5 23.4 ± 3.4 0.290\nAdenomyosis volume (cm\n3\n) 83.3 (41.7–164.9) 96.4 (56.7–203.7) 0.600\nTypes of adenomyosis (diffuse/focus) 98/20 28/12 0.076\nPosition involved in uterus\nAnterior (yes/no) 59/59 17/23 0.412\nPosterior (yes/no) 77/41 28/12 0.451\nFundus (yes/no) 43/75 13/27 0.653\nNPV (cm\n3\n) 43.5 (19.7–80.6) 49.9 (28.9–104.4) 0.300\nSonication power (W) 400 (385–400) 400 (369–400) 0.064\ntreatment time (min) 78.3 ± 55.5 80.8 ± 40.0 0.006\n�\nSonication time (s) 841.2 ± 544.4 1004.1 ± 670.6 0.019\n�\nSonication dose (kJ) 331.3 ± 216.4 386.5 ± 260.3 0.055\nEEF (kJ/cm\n3\n) 2.4 (1.5–7.8) 2.9 (1.9–4.6) 0.015\n�\nNPVR (%) 50.7 (40.1–67.1) 58.0 (38.0–75.2) 0.145\nIT (d) 1 (1–2) 5 (2–7) 0.000\n�\nBMI: body mass index; EEF: energy efficiency factor; IT: interval time between HIFU procedure and MRI scanning post-treatment.\nTable 7. Comparison of clinical and treatment parameters between DWI-subtype IIa and DWI-subtype IIb group.\nAblation subtypes on DWI\npSubtype IIa Subtype IIb\nAge 43 ± 4 38 ± 7 0.604\nBMI 23.1 ± 2.1 22.5 ± 2.7 0.277\nAdenomyosis volume (cm\n3\n) 88 (57.5–260.9) 98.6 (51.7–175.3) 0.064\nTypes of adenomyosis (diffuse/focus) 99/21 39/15 0.122\nPosition involved in uterus\nAnterior (yes/no) 62/58 25/29 0.512\nPosterior (yes/no) 77/43 38/16 0.424\nFundus (yes/no) 45/75 18/36 0.597\nNPV (cm\n3\n) 52.6 (21–113.5) 54.6 (19.3–83.2) 0.013\n�\nSonication power (W) 400 (373–400) 398 (371–400) 0.013\n�\ntreatment time (min) 78.0 ± 54.6 83.3 ± 37.1 0.326\nSonication time (s) 870 ± 477 784 ± 483 0.172\nSonication dose (kJ) 353.7 ± 181 309 ± 187.5 0.241\nEEF (kJ/cm\n3\n) 2.6 (1.2–7.9) 3.1 (1.6–4.3) 0.881\nNPVR (%) 44.1 (35.8–68.5) 67.7 (35.2–79.5) 0.026\n�\nIT (d) 1 (1–3) 6 (3–6) 0.000\n�\nBMI: body mass index; EEF: energy efficiency factor; IT: interval time between HIFU procedure and MRI scanning post-treatment.\nINTERNATIONAL JOURNAL OF HYPERTHERMIA\n 7\n\nstatistically different from their corresponding NPV. Neither \nV\nDWI \nof type I nor V\nDWI \ntype II V\nDWI \ndiffered significantly from \ntheir corresponding NPV. Even though most type I ablation \nareas on DWI were relatively ill-defined, their outlines were \nstill visible, and their V\nDWI \nwas comparable with NPV. For \npatients whose ablation areas were unrecognized, we \ndefined their V\nDWI \nas 0 cm\n3\n. However, no difference was \nfound between their V\nDWI \nand NPV. Because they had rather \nlow NPV (less than 10 cm\n3\n). For these reasons, DWI has high \naccuracy in the volume measurement of ablation areas of all \ntypes. However, T2WI is not suitable for evaluating the effi -\nciency of HIFU treatment for adenomyosis independently, \nconsidering the limited accuracy of volume measurement for \nablation areas. The classification of ablation area types on \nT2WI and DWI between two radiologists reached “fairly \ngood” standards (j ¼ 0.627 and 0.651) in Kappa consistency \ntests. This meant that a “gray zone” existed in the classifica -\ntion of area types on DWI. However, it may have little effect \non the value of DWI in efficiency evaluation, because DWI \nachieved high accuracy in the measurement of ablation areas \nof both type I and type II. Based on the above analysis, we \nbelieve that DWI may replace CE-T1WI in NPVR measure -\nments and calculations to some extent.\nThere are still some limitations in this study: first, it is a \nretrospective study, and bias is inevitable; furthermore, the \ninterval time of MRI reexamination post-treatment for some \npatients exceeded 2 days, which may have some impact on \nthe results; and finally, patients were treated by physicians \nwith different seniorities.\nConclusions\nBoth T2WI and DWI have the potential to evaluate the effi -\nciency of high-intensity focused ultrasound in adenomyosis \nablation, and DWI may be an alternative to CE-T1WI.\nAuthor contributions\nSi Ma: manuscript writing, data management, and analysis. Mingmei \nTang, Xueke Qiu, and Yang Liu (third author): Classification and ROI \ndelineation. Chunmei Gong: Conceptualization. Yan Hu: chart drawing. \nFajin Lv and Yang Liu: project development and administration.\nEthical approval\nThe protocol of this retrospective study was approved by the Ethics \nCommittee, and the requirement for informed consent was waived (eth -\nics approval number K2023-115). All patient data were anonymized for \nreporting purposes.\nDisclosure statement\nNo potential conflict of interest was reported by the author(s).\nFunding\nThe authors reported there is no funding associated with the work fea -\ntured in this article.\nData availability statement\nThe authors confirm that data supporting the findings of this study are \navailable upon request from the corresponding author. The data are not \npublicly available because they contain information that can comprom -\nise the privacy of the research participants.\nReferences\n0[1] Zhai J, Vannuccini S, Petraglia F, et al. Adenomyosis: mechanisms \nand pathogenesis. Semin Reprod Med. 2020;38(2-03):129–143. \ndoi: 10.1055/s-0040-1716687.\n0[2] Chen Q, Li YW, Wang S, et al. Clinical manifestations of adeno -\nmyosis patients with or without pain symptoms. J Pain Res. 2019; \n12:3127–3133. doi: 10.2147/JPR.S212117.\n0[3] Harada T, Khine YM, Kaponis A, et al. The impact of adenomyosis \non women’s fertility. Obstet Gynecol Surv. 2016;71(9):557–568. \ndoi: 10.1097/OGX.0000000000000346.\n0[4] Bachu VS, Kedda J, Suk I, et al. High-intensity focused ultrasound: \na review of mechanisms and clinical applications. Ann Biomed \nEng. 2021;49(9):1975–1991. doi: 10.1007/s10439-021-02833-9.\n0[5] Marques ALS, Andres MP, Kho RM, et al. Is high-intensity focused \nultrasound effective for the treatment of adenomyosis? A system -\natic review and meta-analysis. J Minim Invasive Gynecol. 2020; \n27(2):332–343. doi: 10.1016/j.jmig.2019.07.029.\n0[6] Ou KY, Jeng CJ, Long CY, et al. A comparison of the cost-utility \nof ultrasound-guided high-intensity focused ultrasound and hys -\nterectomy for adenomyosis: a retrospective study: is the cost- \neffectiveness of HIFU for adenomyosis and fibroids feasible? \nBJOG. 2018;125(6):763–764. doi: 10.1111/1471-0528.15115.\n0[7] Fan TY, Zhang L, Chen W, et al. Feasibility of MRI-guided high \nintensity focused ultrasound treatment for adenomyosis. Eur J \nRadiol. 2012;81(11):3624–3630. doi: 10.1016/j.ejrad.2011.05.036.\n0[8] Mindjuk I, Trumm CG, Herzog P, et al. MRI predictors of clinical \nsuccess in MR-guided focused ultrasound (MRgFUS) treatments \nof uterine fibroids: results from a single Centre. Eur Radiol. 2015; \n25(5):1317–1328. doi: 10.1007/s00330-014-3538-6.\n0[9] Keserci B, Duc NM. Magnetic resonance imaging features influ -\nencing high-intensity focused ultrasound ablation of adenomyo -\nsis with a nonperfused volume ratio of �90% as a measure of \nclinical treatment success: retrospective multivariate analysis. Int J \nHyperthermia. 2018;35(1):626–636. doi: 10.1080/02656736.2018. \n1516301.\n[10] Prince MR, Zhang H, Zou Z, et al. Incidence of immediate gado -\nlinium contrast media reactions. AJR Am J Roentgenol. 2011; \n196(2):W138–W143. doi: 10.2214/AJR.10.4885.\n[11] Rogosnitzky M, Branch S. Gadolinium-based contrast agent tox -\nicity: a review of known and proposed mechanisms. Biometals. \n2016;29(3):365–376. doi: 10.1007/s10534-016-9931-7.\n[12] Laurent S, Elst LV, Copoix F, et al. Stability of MRI paramagnetic \ncontrast media: a proton relaxometric protocol for transmetalla -\ntion assessment. Invest Radiol. 2001;36(2):115–122.  doi: 10.1097/ \n00004424-200102000-00008.\n[13] Liao D, Xiao Z, Lv F, et al. Non-contrast enhanced MRI for assess -\nment of uterine fibroids’ early response to ultrasound-guided \nhigh-intensity focused ultrasound thermal ablation. Eur J Radiol. \n2020;122:108670. doi: 10.1016/j.ejrad.2019.108670.\n[14] Ikink ME, Voogt MJ, van den Bosch MA, et al. Diffusion-weighted \nmagnetic resonance imaging using different b-value combina -\ntions for the evaluation of treatment results after volumetric \nMR-guided high-intensity focused ultrasound ablation of uterine \nfibroids. Eur Radiol. 2014;24(9):2118–2127. doi: 10.1007/s00330- \n014-3274-y.\n[15] Liu J, Wei J, Keserci B, et al. T2\n�\n-weighted imaging in the assess -\nment of the non-perfused volume of uterine fibroids following \nmagnetic resonance-guided high-intensity focused ultrasound \nablation. Int J Gynaecol Obstet. 2016;132(1):100–102. doi: 10. \n1016/j.ijgo.2015.07.005.\n8\n M. SI ET AL.\n\n[16] Wu F, Chen WZ, Bai J, et al. Tumor vessel destruction resulting \nfrom high-intensity focused ultrasound in patients with solid \nmalignancies. Ultrasound Med Biol. 2002;28(4):535–542. doi: 10. \n1016/s0301-5629(01)00515-4.\n[17] Gong C, Lin Z, Lv F, et al. Magnetic resonance imaging parame -\nters in predicting the ablative efficiency of high-intensity focused \nultrasound for uterine fibroids. Int J Hyperthermia. 2021;38(1): \n523–531. doi: 10.1080/02656736.2021.1904152.\n[18] Gong C, Yang B, Shi Y, et al. Factors influencing the ablative effi -\nciency of high intensity focused ultrasound (HIFU) treatment for \nadenomyosis: a retrospective study. Int J Hyperthermia. 2016; \n32(5):496–503. doi: 10.3109/02656736.2016.1149232.\n[19] Chu KF, Dupuy DE. Thermal ablation of tumours: biological mech -\nanisms and advances in therapy. Nat Rev Cancer. 2014;14(3):199– \n208. doi: 10.1038/nrc3672.\n[20] Willis WT, Jackman MR, Bizeau ME, et al. Hyperthermia impairs \nliver mitochondrial function in vitro. Am J Physiol Regul Integr \nComp Physiol. 2000;278(5):R1240–R1246. doi: 10.1152/ajpregu. \n2000.278.5.R1240.\n[21] Harary M, Essayed WI, Valdes PA, et al. Volumetric analysis of \nmagnetic resonance-guided focused ultrasound thalamotomy \nlesions. Neurosurg Focus. 2018;44(2):E6. doi: 10.3171/2017.11. \nFOCUS17587.\n[22] Walker MR, Zhong J, Waspe AC, et al. Acute MR-guided high- \nintensity focused ultrasound lesion assessment using diffusion- \nweighted imaging and histological analysis. Front Neurol. 2019; \n10:1069. doi: 10.3389/fneur.2019.01069.\n[23] Gomori JM, Grossman RI, Goldberg HI, et al. Intracranial hemato -\nmas: imaging by high-field MR. Radiology. 1985;157(1):87–93. doi: \n10.1148/radiology.157.1.4034983.\n[24] Gomori JM, Grossman RI, Hackney DB, et al. Variable appearances \nof subacute intracranial hematomas on high-field spin-echo MR. \nAm J Roentgenol. 1988;150(1):171–178. doi: 10.2214/ajr.150.1.171.\n[25] Jacobs MA, Gultekin DH, Kim HS. Comparison between diffusion- \nweighted imaging, T2-weighted, and postcontrast T1-weighted \nimaging after MR-guided, high intensity, focused ultrasound \ntreatment of uterine leiomyomata: preliminary results. Med Phys. \n2010;37(9):4768–4776. doi: 10.1118/1.3475940.\n[26] Pilatou MC, Stewart EA, Maier SE, et al. MRI-based thermal dosim -\netry and diffusion-weighted imaging of MRI-guided focused ultra -\nsound thermal ablation of uterine fibroids. J Magn Reson \nImaging. 2009;29(2):404–411. doi: 10.1002/jmri.21688.\nINTERNATIONAL JOURNAL OF HYPERTHERMIA\n 9","source_license":"CC0","license_restricted":false}