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Computed tomography and magnetic resonance imaging findings in dogs with vaginal leiomyoma and leiomyosarcoma

Abstract Background In humans, magnetic resonance imaging (MRI) is preferred over computed tomography (CT) for the assessment of pelvic lesions. Although CT findings of several pelvic tumours have been reported in veterinary medicine, MRI findings are limited. Objectives The purpose of this study was to retrospectively compare the CT and MRI findings in dogs with vaginal leiomyoma and leiomyosarcoma. Methods This retrospective study of five dogs compared the CT and MRI findings of intrapelvic lesions, including vaginal leiomyoma (n = 4) and leiomyosarcoma (n = 1). No invasion of the surrounding tissue was detected on histopathological examination. In this retrospective study, the following parameters of CT and MRI were recorded for each dog: the border between the lesion and the adjacent pelvic organs, including the prostate, rectum or urethra; signal intensity (SI) of the lesion; enhancement pattern; presence of haemorrhage; necrosis or cystic areas and lymphadenopathy. Because SI on MRI is affected by cell density, tumour cell density was analysed using a microscope slide. Results In vaginal leiomyoma, the border between the lesion and the surrounding pelvic organ tends to be clearer on MRI than on CT. In vaginal leiomyosarcoma, the border was comparable between MRI and CT. Each lesion showed heterogeneous enhancement on CT and MRI scans. In each lesion, the assessment of haemorrhage, necrosis, cystic areas and lymphadenopathy was comparable between MRI and CT. The SI of the lesion on T2WI of the vaginal leiomyoma and leiomyosarcoma were hyperintense in four cases (4/4; 100%) and mixed intense in one case (1/1; 100%), respectively. The cell density of leiomyosarcoma is higher than that of leiomyomas. Conclusions The SI on T2WI may be useful for differentiating leiomyoma from leiomyosarcoma. MRI may be useful to differentiate vaginal leiomyomas from leiomyosarcomas and evaluate margins.


INTRODUCTION
In veterinary medicine, computed tomography (CT) is performed for the purpose of several tumour diagnoses and staging (Forrest, 2016). Magnetic resonance imaging (MRI) is performed for pelvic tumours, including prostate adenocarcinoma, although in limited numbers (Tanaka et al., 2020). MRI examinations are expensive compared to CT, require more extended anaesthesia, and have limited facilities.
Therefore, it may be necessary to compare the findings of CT and MRI to understand their characteristics and select the appropriate examination modality.
In humans, various modalities have been used to assess pelvic lesions. MRI is preferred over CT for pelvic lesions because of superior soft tissue contrast compared to CT (Laval-Jeantet et al., 1985;Ng et al., 1997;Park, 2014) .Because signal intensity (SI) on MRI is affected by cell density in the lesion, MRI is useful in differentiating benign from malignant lesion (Som & Biller, 1989). MRI allows visualization of the rectum, urinary bladder, and internal genitalia with high soft-tissue contrast (Blomqvist et al., 2002). Pelvic tumours arise from the rectum, nerves, blood vessels, glands and adipose tissue (Spector et al., 2011).
In veterinary medicine, CT findings of several pelvic tumours have been reported (Spector et al., 2011;Tanaka et al., 2021). Full-body CT is a suitable imaging modality when pelvic tumours are suspected (Ferraris et al., 2021). Because of the limited volume of the pelvic cavity, large masses compress the adjacent organs. To the best of our knowledge, information regarding pelvic lesions using MRI is limited. Therefore, we hypothesized that MRI would be more useful than CT for assessing pelvic lesions. Therefore, we aimed to compare the CT and MRI findings in dogs with pelvic lesions, including vaginal leiomyoma and vaginal leiomyosarcoma.

F I G U R E 1
Interpretation of the procedure. The source microscopic image (a; H&E stain) was divided into three primary colour images (red, green, and blue) (b). Then, the threshold was defined for tumour cell nuclei, and the nuclear area was extracted (c).
Various qualitative parameters were recorded during image analysis: the border between the lesion and the adjacent pelvic organs, including the prostate, rectum or urethra on CT and MRI (clear or unclear); the SI of the lesion on MRI, including T2WI and pre-contrast T1WI (hyper-, iso-, hypo-, mixed-); enhancement pattern of the lesion on CT and MRI (homogeneous or heterogeneous); haemorrhage in the lesion on CT and MRI (present or absent); necrosis or cystic areas in the lesion on CT and MRI (present or absent); lymphadenopathy on CT and MRI (present or absent) and pulmonary metastasis on CT (present or absent).
The border was defined as the boundary between the lesion and the adjacent pelvic organ. It was classified as clear if the organ structures and boundaries bordering the tumour were clear. On MRI, the border was evaluated using T2WI and post-contrast T1WI. The SI of the lesion was assessed, excluding the cystic and necrotic areas. The SI on T2WI and pre-contrast T1WI was subjectively compared between the lesion and skeletal muscle. If several degrees of SI were detected, the SI was defined as mixed intensity. For the enhancement pattern (homogeneous or heterogeneous) on CT, the enhancement pattern of lesions in the equilibrium phase was considered homogeneous or heterogeneous depending on whether there was less or more than 10 HU difference in enhancement present in the lesions (Zhu et al., 2012). On MRI, the enhancement pattern was considered subjectively depending on homogeneous or heterogeneous SI change compared between pre-and post-contrast T1WI (Sadohara et al., 2006). Haemorrhage was defined as an unenhanced area and/or area containing high attenuation value within the lesion seen on pre-contrast-enhanced CT (Sadohara et al., 2006). On MRI, haemorrhage was defined as an unenhanced area and an area that contained high-signal intensity on both T2WI and T1WI, although haemorrhage showed various signal intensities due to bleeding within the tumour (Griffin et al., 2008;Kalisz et al., 2021;Sadohara et al., 2006). Necrosis or cystic areas was defined as an unenhanced area and/or an area of decreased attenuation seen within the lesion on CT, and an unenhanced area and/or an area of low-signal intensity observed on T1WI and high-signal intensity on T2WI on MRI (Sadohara et al., 2006). Lymphadenopathy was defined as when greater than reported normal lymph nodes (Beukers et al., 2013). Lymphadenopathy was assessed for the medial iliac, internal iliac and sacral lymph nodes.
Tumour cell density was analysed based on a previous report (Tasaki et al., 2015). Cell density was analysed by excluding necrotic areas using ImageJ software (NIH, Bethesda, MD, USA). Microscopic images were randomly obtained from different regions of each tumour section ( Figure 1a). Red, green and blue colour spreads were processed for each image, and the red image in which the cell nucleus was most marked was selected (Figure 1b). A threshold was defined to extract tumour cell nuclei (Figure 1c). Based on this threshold, cell density was calculated by dividing the total area of the tumour cell nuclei by the entire area of the microscopic image.

RESULTS
A total of 22 dogs satisfied our initial criteria; of these, five met the Leiomyosarcoma indicated heterogeneous enhancement on CT and MRI and mixed signal intensity (hypo-to isointense) on T2WI. CT, computed tomography; MRI, magnetic resonance imaging; T2WI, T2-weighted imaging; T1WI, T1-weighted imaging.

F I G U R E 4
Representative images of the border between leiomyoma and rectum (a, b) or urethra (c, d) on MR images in T2WI and CT images in portal phase post-contrast. Vaginal leiomyoma indicated a clear border between the lesion and rectum or urethra on MRI (a, c, arrowhead) compared to CT (b, d, arrowhead). CT, computed tomography; MRI, magnetic resonance imaging; T2WI, T2-weighted imaging.

DISCUSSION
In this study, MRI was superior to CT in assessing clear boundary between the tumour and adjacent organs. This may be due to the loss of contrast caused by the absence of fat between the tumour and the adjacent organs on CT. In humans with low anterior rectal tumours, CT cannot assess tumour infiltration as accurately as MRI because the lack of a fatty layer between the tumour and the surrounding mesentery makes the poor differentiation of rectal wall (Dar et al., 2014;Maizlin et al., 2010). On CT, the limiting factor is tissue differentiation (Follen et al., 2003). In humans, T2WI provides excellent detail of normal tissue anatomy and detects the internal structure of tumour (Follen et al., 2003). Our results indicated clear, detailed tissue anatomy and the relationship between tumour and adjacent tissue on T2WI. Therefore, T2WI may be used to evaluate the margins of the primary tumour. Unfortunately, this study did not include cases of tumour invasion into adjacent organs. Further investigation of the invasion of pelvic lesions into adjacent organs in a large population of dogs is required. In this study, there was no difference in the detection of haemorrhage, necrosis, cystic areas or lymphadenopathy between CT and MRI. In this study, T2*WI was not performed to assess haemorrhage on MRI. T2*WI may improve the detection rate of haemorrhage, because T2*WI detects even small haemorrhages as low-signal foci and is the most sensitive sequence for detecting haemorrhagic debris T2WI, T2-weighted imaging; T1WI, T1-weighted imaging. (Atlas, 2009;Cordonnier et al., 2007). In humans, MRI is superior to CT in depicting the capsule, septum and haemorrhage within the tumour (Sadohara et al., 2006). Therefore, MRI may be useful for a detailed structural evaluation. In humans, MRI is superior to CT in evaluating tumour extension and lymphadenopathy (Laval-Jeantet et al., 1985).
Conversely, CT is more useful in detecting distant metastases (Horvat et al., 2019). In this study, no metastases were observed in all dogs.
Unfortunately, this study included a limited number of patients with pelvic lesions. Further studies are needed to determine the selection criteria for CT and MRI scans.
MRI is currently considered the gold standard for imaging in humans, as leiomyomas can be differentiated from malignant vaginal tumours, such as leiomyosarcomas, based solely on their MRI characteristics (Demulder & Ascher, 2018). In humans, vaginal leiomyomas appear as hypointense lesions on T2WI compared to the skeletal mus-cle (Park, 2014;Shadbolt et al., 2001;Siegelman & Outwater, 1999;Thomassin-Naggara et al., 2008;Togashi et al., 1989). Vaginal leiomyomas occasionally undergo degeneration (Griffin et al., 2008). The SI of leiomyomas varies depending on the degeneration of the cellular contents (Yamashita et al., 1993). Myxoid and cystic degeneration is seen as hyperintense on T2WI, while haemorrhagic degeneration appears as hyperintense on both T1WI and T2WI (Griffin et al., 2008;Namimoto et al., 2009). Hyaline degeneration and abundant collagenous tissue are seen as areas of hypointense on T2WI, compared to skeletal muscle (Marinelli et al., 2007;Namimoto et al., 2009;Shuto et al., 2002). In veterinary medicine, MRI of the vaginal masses is not reported (Russo et al., 2021). In this study, leiomyoma was seen as hyperintense lesions on T2WI as compared to the skeletal muscle. This finding differs from that observed in humans. Necrosis and cystic areas were present in all cases. Moreover, in these dogs, histopathologically, vaginal leiomyomas did not show degeneration, including hyaline degeneration and collagenous tissue changes. The SI of leiomyoma on T2WI may be influenced by histopathological changes.
In this study, the SI of leiomyosarcoma on T2WI was mixed, including hypointense areas, compared to that of leiomyomas. The cell density of leiomyosarcoma was higher than that of leiomyomas. Decreased SI on T2WI in malignant tumours is caused by a high cell density, which causes a reduction in mobile protons (Som & Biller, 1989). Therefore, the SI of leiomyosarcoma may be lower than that of leiomyoma. On CT and MRI, leiomyomas and leiomyosarcomas showed heterogeneous enhancement. A previous report indicated that leiomyomas show internal homogeneity on CT, which is useful in differentiating benign from malignant tumours (Spector et al., 2011). However, our results differed from those of previous reports. In humans, heterogeneous enhancement is caused by haemorrhage, necrosis and calcification (Agah et al., 2017). In this study, necrosis or cystic areas were present in leiomyoma, which may have affected the enhancement pattern. However, the enhancement pattern may not differentiate leiomyomas from leiomyosarcomas. Therefore, the SI on T2WI may be useful for differentiating leiomyoma from leiomyosarcoma. In this study, no CT findings could differentiate leiomyomas from leiomyosarcomas. However, the MRI findings showed the possibility of differentiation. Therefore, MRI may be useful in differentiating leiomyomas from leiomyosarcomas.
This study had some limitations. First, this study included a small number of dogs with a limited distribution of tumour types. In particular, malignant tumours that invaded the adjacent organs were not assessed. Second, this study was performed with a limited sequence type of MRI. The structural evaluation may be more accurate using several sequences, including fat-suppressed, thin-sliced 3D, and T2* sequences. Further studies are needed to determine the appropriate MRI sequence that would be the most useful for structural evaluation.
In conclusion, MRI, including T2WI and post-contrast T1WI, was superior to CT in assessing clear boundary between the tumour and adjacent organs. Therefore, MRI may be used to evaluate the margins of the primary tumour without a contrast agent. In addition, T2WI may be useful for differentiating vaginal leiomyoma from leiomyosarcoma.

AUTHOR CONTRIBUTIONS
Toshiyuki Tanaka: Conceptualization, data curation, formal analysis, investigation, project administration, validation, visualization and writing-original draft.
Shunsuke Noguchi: writing-review and editing.
Yusuke Wada: formal analysis, writing-review and editing.
Hiroki Yamazaki: writing-review and editing.
Hidetaka Nishida: writing-review and editing.