MRI of bladder cancer - Local and nodal staging Iztok Caglic, MD, PhD,1 Valeria Panebianco, MD, PhD,2 Hebert A. Vargas, MD,3 Vlad Bura, MD, 4 Sungmin Woo, MD, PhD,3 Martina Pecoraro, MD,2 Stefano Cipollari, MD,2 Evis Sala, MD, PhD,1*, Tristan Barrett, MD1* 1) Department of Radiology, Addenbrooke’s Hospital and University of Cambridge, Cambridge, UK 2) Department of Radiological, Oncological and Anatomo-pathological sciences, "Sapienza University", Rome, Italy 3) Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA 4) Department of Radiology, County Clinical Emergency Hospital, Cluj-Napoca, Romania *Joint senior authors Corresponding author Iztok Caglic (email: iztokcaglic@gmail.com, phone: +447402 108162) Department of Radiology, Addenbrooke’s Hospital and University of Cambridge, Cambridge, CB2 0QQ, UK Acknowledgements: Authors IC, TB and ES acknowledge research support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre. Running title: MRI Staging in Bladder Cancer MRI of bladder cancer - Local and nodal staging Abstract Accurate staging of bladder cancer (BC) is critical, with local tumour staging directly influencing management decisions, and affecting prognosis. However, clinical staging based on clinical examination including cystoscopy and transurethral resection of bladder tumour often under-stages patients compared to final pathology at radical cystectomy and lymph node dissection, mainly due to underestimation of the depth of local invasion and presence lymph node metastasis. MRI has now become established as the modality of choice for the local staging of BC and can be additionally utilized for the assessment of regional lymph node involvement and tumour spread to the pelvic bones and upper urinary tract. The recent development of the Vesical Imaging-Reporting And Data System (VI-RADS) recommendations has led to further improvements in bladder MRI, enabling standardization of image acquisition and reporting. Multiparametric MRI (mpMRI) incorporating morphological and functional imaging has been proven to further improve the accuracy of primary and recurrent tumour detection and local staging, and has shown promise in predicting tumour aggressiveness and monitoring response to therapy. These sequences can also be utilised to perform radiomics which has shown encouraging initial results in predicting BC grade and local stage. In this article, the current state of evidence supporting MRI in local, regional and distant staging in patients with bladder cancer is reviewed. Keywords: Multiparametric MRI, Bladder cancer, Staging Abbreviations 2D Two dimensional 3D Three dimensional ADC Apparent diffusion coefficient AJJC American Joint Committee on Cancer AUC Area under the curve BC Bladder cancer BS Bone scintigraphy CT Computed tomography CTU Computed tomography urography DCEI Dynamic contrast enhanced imaging DWI Diffusion weighted imaging EPI Echo planar imaging FOV Field of view FSE Fast spin echo GRE Gradient echo HBB Hyoscine butylbromide LN Lymph node MIBC Muscle invasive bladder cancer MpMRI Multiparametric magnetic resonance imaging NMIBC Non-muscle invasive bladder cancer MRI Magnetic resonance imaging MRL Magnetic resonance lymphangiography MRU Magnetic resonance urography NAC neoadjuvant chemotherapy NEX Number of excitations pCR Pathologic complete response PROPELLER Periodically rotated overlapping parallel lines with enhanced reconstruction SE Spin echo SI Signal SNR Signal-to-noise ratio SV Seminal vesicles T2W T1-weighted T1W T2-weighted TNM Tumour, Node and Metastasis TURBT Transurethral resection of bladder tumour USPIO Ultra-small superparamagnetic iron oxide UUT Upper urinary tract VI-RADS Vesical Imaging-Reporting And Data System Introduction Bladder cancer (BC) is the second most common genitourinary malignancy after prostate cancer and the 10th commonest cancer worldwide, with an estimated over 540,000 new cases and 200.000 deaths per year (1). The incidence of BC increases with age and is approximately 3-4 times higher in men, with tobacco smoking being the greatest risk factor, accounting for about 50% of cases (2). Urothelial carcinoma accounts for approximately 90% of BC cases; with squamous cell carcinoma (6-8%) and adenocarcinoma (2%) being rare subtypes (3). The majority of patients (70%) present with non-muscle invasive BC (NMIBC) which has a more favorable prognosis than tumours that invade into the detrusor muscle of the bladder wall: muscle invasive BC (MIBC), however, the high rate of recurrence and disease progression requires a robust long-term follow-up and results in the highest lifetime treatment costs per patient compared to all cancer groups (4). The most common presenting symptoms in patients with BC are painless haematuria and/or less commonly lower urinary tract symptoms including dysuria, urgency and frequency; pelvic pain and urinary obstruction are generally limited to advanced disease (3). The traditional diagnostic workup relies on clinical examination, cystoscopy and transurethral resection of bladder tumour (TURBT) to confirm histopathological diagnosis and muscle invasiveness, with computed tomography (CT) typically reserved for evaluation of locally advanced disease, N- and M-stage (5, 6). Accurate staging is critical, as prognosis and management of patients with BC largely depends on the local tumour stage and presence of lymph node or distant metastases (5–7). However, there is a substantial discrepancy between preoperative clinical staging (combined bimanual examination, TURBT and conventional imaging) and the final pathologic staging based on radical cystectomy and lymph node dissection with an inaccuracy rate of 23-50%, mainly due to under-staging of both the depth of local invasion and lymph node metastatic involvement (8, 9). Magnetic resonance imaging (MRI) is being increasingly used for the pre-operative, local staging of BC due to its high soft tissue contrast resolution, and ability to assess the depth of bladder wall invasion, with a recent meta-analyses reporting a high diagnostic performance in differentiating NMIBC from MIBC, as well as for predicting extravesical extension (10–14). Multiparametric MRI (mpMRI) which incorporates morphological T2-weighted imaging (T2W) alongside the functional sequences of diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) imaging has been proven to further improve accuracy of primary and recurrent tumour detection and local staging, and has shown promise in monitoring treatment response (10–12, 15–17). MRI can be additionally utilized for the assessment of regional lymph node involvement and tumour spread to the pelvic bones and upper urinary tract (UUT). However, sensitivity for detecting lymph node metastases remains unsatisfactory due to an over-reliance on size criteria (18). Regarding UUT evaluation, CT urography (CTU) is generally recommended as the first line investigation, however, magnetic resonance urography (MRU) has a good sensitivity for depicting UUT tumours and is used when CTU is contraindicated (6, 19), or as part of an all-in-one assessment of the urinary tract in high risk disease. In this review, we describe the optimal protocols for MR image acquisition, cover recent updates in image interpretation, describe the role of MRI in local, regional and distal staging of bladder cancer, and summarize the added value of bladder mpMRI in assessment of treatment response. Bladder anatomy and TNM staging The bladder is a hollow organ of the lower urinary tract system located extra peritoneally in the lower anterior pelvis and surrounded by perivesical fat. Its wall consists of 1) urothelium, the innermost epithelial layer, 2) subepithelial connective tissue (lamina propria), containing blood vessels, lymphatics and the thin and incomplete muscularis mucosa, 3) muscularis propria - also known as detrusor muscle which is composed of inner and outer smooth muscle, and 4) loose connective tissue of the adventitia (20). On T2W or DW imaging, however, only the muscularis propria is typically identified, either as a low signal intensity band, or a thin line of intermediate signal intensity, respectively. At DCE imaging, the inner layer of mucosa (which includes the urothelium and lamina propria with muscularis mucosa) shows early enhancement and can thus be differentiated from the underlying muscularis propria (outer layer), which demonstrates delayed enhancement (13). Therefore, from a radiological perspective there are three basic layers of mucosa, detrusor muscle and perivesical fat which can be distinguished, all being essential for local bladder cancer staging. The Tumour, Node and Metastasis (TNM) system is employed for staging of bladder cancer, originally developed by the American Joint Committee on Cancer (AJCC) and last updated in 2017 (8th edition) (21). Local T-stage is defined by the depth of tumour invasion into the deep layers of the bladder wall and surrounding tissues. NMIBC is subclassified into Ta (noninvasive papillary carcinoma), Tis (noninvasive carcinoma in-situ) and T1 stage (invasion of lamina propria). MIBC is subdivided into T2a (invasion of inner half of the detrusor muscle) and T2b disease (invasion of the outer half of the detrusor muscle). Of note, according to the eighth edition of TNM classification, there is no T2 stage when cancer arises within bladder diverticuli, as these are classically acquired pseudodiverticuli, and lack a muscle layer (20, 22) (Figure 1). Locally advanced disease recognizes microscopic (T3a) and macroscopic (T3b) invasion of the perivesical fat. T4 stage indicates cancer has spread to the surrounding pelvic organs, pelvic or abdominal wall (21). N-stage is defined by involvement of regional lymph nodes (N1-N3) and is described in detail in the corresponding section below, whilst M-stage constitutes either involvement of non-regional lymph nodes (M1a) or distant metastases (M1b) (Supplemental table 1). In addition to TNM stage, the final treatment decisions depend on the grade of cancer which is histologically stratified into low- and high-grade papillary urothelial carcinomas according to the 2004 WHO classification (23). MRI Protocol MRI of the urinary bladder necessitates high-resolution images with a high signal-to-noise ratio. This may be achieved at either 1.5T or 3T, with a multichannel phase-array surface coil with at least 16-channels being mandatory. Localizer sequences serve to ensure correct positioning of the surface coil and adequate bladder distension, and to plan coverage for the initial high resolution sequences. An appropriate field-of-view (FOV) should be selected, including the entire bladder and incorporating surrounding structures such as pelvic lymph nodes, the proximal urethra, pelvic bones, the prostate and seminal vesicles in men, and gynaecological organs in female patients (24). A multiparametric (mp) approach combining anatomical and functional sequences is recommended for urinary bladder cancer detection and staging. The mpMRI protocol should incorporate multiplanar T2W, DWI, dynamic contrast-enhanced images (DCE-MRI) and T1- weighted (T1W) imaging (7) (Table 1). Findings on T2W, DCE and DWI should always be correlated and evaluated altogether, to acknowledge any inter-sequence mismatch, that could lead to erroneously up-staging or down-staging of tumors. Numerous studies have highlighted the improved sensitivity, specificity and accuracy when two or more sequences are used for the diagnosis and staging of BC (25–27); DWI in particular, with its limited spatial resolution, should always be analyzed in conjunction with anatomical sequences (Figure 2). T1WI and T2WI T1W spin-echo (SE) images are acquired in the axial plane employing a large FOV which should cover the entire pelvis from the aortic bifurcation to the symphysis pubis. Whilst T1WI plays a minor role in local staging, it is useful to assess for blood products within the bladder, lymphadenopathy and bone metastases; urine, bladder wall and perivesical fat will demonstrate, respectively, low, intermediate and high signal intensity. Two-dimensional (2D) fast-spin-echo (FSE) T2WI or turbo-spin-echo thin sections (3-4 mm) sequences are acquired employing a small FOV and a large matrix, in three orthogonal planes (axial, coronal and sagittal). On T2W images, urine is of high signal intensity, and the bladder wall demonstrates a low signal intensity (Table 2). Having high resolution T2W imaging in three planes is fundamental in order to accurately assess T-staging. Selection of the most appropriate plane (the one most perpendicular to the wall being assessed) primarily depends on the location of the tumour to accurately visualize its relation to the bladder wall and perivesical fat and to minimize partial voluming effects. For instance, for the assessment of tumours located in the dome either coronal or sagittal images are preferred to the axial plane. An additional plane, perpendicular to the tumor may also be acquired to assess for muscle invasion, or alternatively derived as a multiplanar reformatted sequence when T2W imaging is performed using isotropic three-dimensional (3D) acquisition (28, 29). Correction of the echo time (60–80 msec) enables a high contrast-to-noise ratio, and allows for full evaluation of depth of muscle invasion (3). DWI DWI sequences are obtained to study the Brownian motion of water molecules and offer useful qualitative and quantitative data on tumor cellularity and cell membrane integrity. Parallel imaging with short echo times, increasing the number of excitations and adjusting the matrix and voxel size are strategies that can help maintain sufficient spatial resolution and appropriate SNR (7). DW images should generally be evaluated alongside T2WI to allow visualization and direct comparison of anatomical structures. DWI is acquired using free-breathing spin-echo (SE) echo-planar imaging (EPI) with spectral fat saturation in two orthogonal planes (axial and either sagittal or coronal). At least two b-value sequences are required to obtain an ADC map, and should include a high-b value of 800-1000 s/mm2 to achieve sufficient contrast resolution compared to surrounding tissues (25). BC shows increased signal intensity on high b-value diffusion-weighted images and a reduced apparent diffusion coefficient (ADC) in contradistinction to the intermediate signal intensity of muscularis propria on b-value imaging and ADC. ADC measurements have been shown to correlate with bladder cancer aggressiveness, therefore showing promise as an imaging biomarker (30–33). Acquisition of good quality images and adequate patient preparation can help avoid “cancer mimics”, particularly relating to motion artefact and susceptibility artefact induced by presence of air (within bladder or bowel) (34) (Figure 3). DCE 3D gradient echo (GRE) sequences are preferred due to a higher spatial resolution, although 2D-T1 GRE is also acceptable; sequences can be acquired either with or without fat suppression (35). Imaging should be obtained before and after gadolinium-based contrast medium injection (0.1 mmol/kg at a rate of 1.5–2.0 mL/s for standard agents), followed by a 20 mL saline flush (36). During the early injection phase (<60 sec) the mucosa and sub-mucosal layers (inner layer) show enhancement and appear of high SI, compared to the relative hypoenhancing bladder muscle (outer layer), which appears of low SI (37). Images are acquired 30s after contrast injection, with a further 4-6 acquisitions at 30s intervals, to detect the early enhancement of tumour/s and mucosa and any extension of tumour into the hypointense muscle layer, which typically enhances later (approximately 20 s versus 60 s after contrast administration, respectively) (13, 27, 38). An alternative is to perform dynamic imaging with a higher temporal resolution (10s intervals), with the potential advantage of being able to extract pharmacokinetic analyses (39). Delayed phase acquisitions are not required for T-staging due to the reducing signal contrast between the different layers of the wall and tumour (7) and due to the presence of high SI contrast agent excreted into the bladder lumen. Patient preparation issues Optimal bladder distension is essential for accurate assessment of bladder tumours at MRI. Over-distension causes thinning of the wall and may reduce sensitivity for detection of flat lesions (40). In addition, over-distension induces bladder wall spasm and is uncomfortable for patients, both of which result in motion artefact (Figure 4). Conversely, under-distension leads to thickening of the detrusor muscle, which may limit the detection of small lesions, or even lead to misinterpretation of mucosal folding as tumour infiltration (27) (Figure 4). There is limited evidence on appropriate bladder filling preparation, but consensus opinion recommends either instructions to void 2h prior to the study with no further oral intake, or drinking 500–1000 ml of water in the 30 min prior to MRI (27, 40). In a recent prospective study, an optimal bladder volume (140-210 mL) was achieved by passing urine 2h prior to MRI exam with no further drinking, however, the additional fluid intake was required for early morning appointments likely due to presence of relative dehydration (41). Small bowel peristalsis can induce motion artefact on MRI, especially on T2WI which tends to be affected more than DWI and DCE (42), some authors therefore recommend use of anti-peristaltic agents such as hyoscine butylbromide (HBB) or glucagon to improve image quality (3, 27, 43, 44). Additional modifications to the imaging acquisition parameters can help mitigate motion artefact, for instance increasing the number of excitations (NEX) and/or changing the phase and frequency-encoding directions (left-to-right for axial imaging) to direct artefact away from the bladder (45). Sampling of k-space by using a combination of rectilinear and radial trajectories has also been shown to reduce motion artefact and increase both image sharpness and overall image quality (46, 47). This MRI technique is known as periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) and has its own disadvantages, including increased acquisition time and reduced overall contrast (48, 49), but may prove useful as a substitute sequence for exams affected by severe motion artefact. Allowing for an adequate time interval following previous intervention is important to enable resolution of reactive inflammatory change within the bladder wall and perivesical fat, which may lead to both false negative and false positive findings (50). A minimum of 2 weeks is recommended after TURBT, bladder biopsy or intravesical therapy, whilst a 2-3 days interval between flexible cystoscopy or removal of Foley catheter is sufficient for re-absorption of air in the bladder which could otherwise cause susceptibility artefacts on DWI (51) (Figure 3). T-staging Accurate local staging of bladder carcinoma is key as it has significant prognostic implications and determines treatment options. Non-muscle invasive bladder carcinomas (Ta-T1) are suitable for localized treatment, either TURBT or intravesical chemotherapy, whilst radical therapy i.e. cystectomy with lymph node dissection remains the gold standard for muscle invasive disease (≥T2) (5–7). In addition, multimodality bladder-preserving treatment combining TURBT, radiotherapy and chemotherapy can be offered to a highly selected group of patients with MIBC (T2 stage and no CIS) (6). According to EAU guidelines the current standard for diagnosis and staging of BC is TURBT (5). However, TURBT may under-stage tumors due to sampling error, particularly if there is an absence of the detrusor layer in the specimen. In addition, up to 25% of T1 tumors are eventually muscle invasive on subsequent TURBT, which entirely changes therapeutic management (52, 53), and over a third of clinically organ-confined BC have been reported to have extravesical extension at final pathology (54). Thus, when high-grade carcinoma is confirmed at initial histology, a repeat surveillance cystoscopy procedure is mandated within 6 weeks of primary resection (5). MRI overcomes such limitations in local staging, with several studies demonstrating that mpMRI represents a reliable tool for differentiating NMIBC from MIBC (55–57) as well as in diagnosing T3 disease (58). In addition, it can further identify MIBC suitable for bladder-sparing therapy and chemoradiation, (unifocal, good bladder capacity) and for the surgical planning of a radical, complete TURBT. To improve acquisition and interpretation of bladder MRI, the Vesical Imaging-Reporting And Data System (VI-RADS) was developed in 2018 by a panel of expert multidisciplinary team members. The guidelines are aimed at accurate staging of disease, given its clinical importance, in contradistinction to PI-RADS (59) which is aimed at detecting prostate tumours, or LI-RADS which attempts to characterize lesions in the cirrhotic liver (60). VI-RADS: Stage T1 versus T2 According to the VI-RADS system (7), each of the three sequences (T2W, DWI and DCE) is scored on a 5-point scale which are then combined to derive an overall VI-RADS score classifying the likelihood of MIBC into five categories (Table 3, 4). Typically, an overall VI-RADS score 1-2 means MIBC is unlikely as opposed to score 4-5 indicating that MIBC is likely. To date, 4 retrospective (14, 61–63) and 1 prospective study (64) have validated the VI-RADS scoring system, demonstrating good performance for identifying MIBC, with area under the curve (AUC) ranging between 0.83-0.94 and a good-to-excellent inter-reader agreement (kappa = 0.72-0.92). Tumor morphology, size, location and integrity of muscularis propria are primarily evaluated on T2W sequence, whilst confirmation of definitive muscular invasion depends on DWI and DCE findings. If there is discordance between T2WI and DCE, then (high quality) DWI should be used as the dominant sequence to improve accuracy (12, 25, 27, 34, 56). Ta - T1 stage tumors can be either sessile or papillary and do not show interruption of the detrusor muscle baseline signal on any of the sequences (Figure 5), whereas T2 tumours should be called when focal disruption of the muscular layer is detected on mpMRI sequences (7) (Figure 6). In addition, the presence of a stalk in an exophytic tumour is an important finding as it may lead to false positive calls, however, this is a reassuring feature described by Takeuchi et al as "inchworm" sign which implies Ta-T1 stage (55). The stalk consists of submucosa with a varying degree of oedema and fibrous change and its T2 signal therefore varies from hypo- to iso- to hyperintensity, however, it does not demonstrate restricted diffusion, appearing of low SI on DWI in contrast to the high SI tumour which surrounds the stalk in a U-shaped configuration (55) (Figure 5). Similarly, overcalling of muscle invasion can be avoided when staging sessile tumours which sometimes show a thickened and inflamed and/or fibrotic submucosa. This exhibits intermediate to low T2 signal but does not restrict diffusion (57), thus the true tumour stands out as a C-shaped structure with high SI on DWI. The TNM system subdivides T2 stage by depth of muscle invasion into T2a (<50%) and T2b stage (≥50%), based on prognosis, with T2b disease carrying a significantly increased risk for lymph node metastasis (14% versus 30%, respectively) resulting in decreased recurrence-free survival after cystectomy (65). However, the therapeutic approach of T2a and T2b disease is similar and as this distinction is challenging on MRI, the VI-RADS system only describes “T2 stage” (51). T2 versus T3 T3 stage is defined as extension of the tumor into the perivesical fat and is further sub-classified into T3a (microscopic – by definition not visualized at MRI) and T3b (macroscopic) extravesical extension (21, 57, 58, 66). TURBT or biopsy specimens cannot be definitive for microscopic extravesical tumor extension (20, 58) as adipocytes are normally seen in between muscle bundles of the outer muscularis propria; thus, interposition of fat with tumor cells in a biopsy or TURBT specimen is at most suggestive of pT3 cancer and accurate T3a categorization can only be assigned on cystectomy specimens (20). Thus, the primary role of MRI staging is to differentiate between the T2 from T3b stage as the management for both T2 and T3a is the same (6, 57). In T3 stage the T2WI and DWI tumour signal extends into the perivesical fat. The outer bladder wall appears ill-defined and irregular and there is associated enhancement (25, 27). In addition, another useful feature to evaluate is the outer contour of the muscle invasive tumour on DWI. If the contour is smooth and regular this implies T2 stage, whereas an irregular and nodular surface suggests T3 disease (57) (Figure 7). T3 versus T4 T4 stage is defined by tumor invasion into adjacent organs, either T4a with extension into the uterus, vagina, prostate or seminal vesicles (SV) (Figure 8) or T4b subcategory incorporating either invasion into the pelvic sidewall or abdominal wall (Figure 9). However, the invaded organ should be clearly stated in the report, given the significant differences in prognosis, for instance prostate versus SV involvement with 5-year survival at 38% and 10%, respectively (67). MRI offers improved evaluation of adjacent organ invasion compared to CT due to a higher soft tissue resolution (58, 66), with a reported accuracy of 96.7% (68). A recent meta-analysis also showed MRI to have superior accuracy compared to clinical staging for differentiating T4b, with a pooled sensitivity of 85% and a specificity of 98% which is helpful when determining the feasibility of resection versus palliative radiation (11). Involvement of adjacent structures should be suspected when there is direct extension of the carcinoma into the adjacent organ with disruption of its normal signal intensity and/or architecture on T2WI. Reference to DCE (early enhancement) and DWI (high signal on b-value imaging and low signal on ADC map) can further increase sensitivity as well as avoid false positive calls (27, 68). Post-interventional appearances When MRI is performed following intervention (post-biopsy or TURBT), subsequent inflammatory changes with bladder wall thickening and perivesical fat stranding may lead to incorrect T-staging (58). A thickened and inflamed oedematous wall will show increased T2 signal intensity and an increased signal intensity on b-value imaging may be mistaken for residual muscle invasive tumour, requiring correlation with ADC maps to confirm T2 shine through effect (15) (Figure 10). In addition, there may be low-to-intermediate T2W signal intensity within the perivesicular fat due to inflammation or fibrosis (38), often accompanied with increased enhancement on DCE, thus mimicking extravesicular T3b disease. However, such changes do not usually demonstrate restricted diffusion and therefore DWI in combination with ADC should be the primary sequences used to differentiate procedure-related inflammatory changes and fibrosis from cancerous spread into the perivesical fat (15, 38). Conversely, a thickened and inflamed wall with secondarily increased enhancement may obscure a small residual lesion (15). N-Staging After tumour T-stage, the nodal status in BC patients is the most significant histopathological prognostic variable (69, 70). Lymph node (LN) involvement significantly correlates with concomitant distant metastases and a marked decrease in 5-year disease free survival (71, 72). The incidence of nodal metastasis closely correlates to tumour stage, with LN metastases being rare for disease stage ≤ T1, but as high as 30% for muscle invasive cancers and 60% when staging is ≥ T3 (66, 73). Lymphadenectomy is therefore standard of care for cystectomy in patients with MIBC (74). Of note, tumor location has been associated with prognosis as there is an increased likelihood of LN involvement with tumours located at the bladder neck or trigone of the bladder due to increased lymphatic and vascular vessels at this site (75). BC spreads primarily to the perivesicular LNs and regional nodal stations within the true pelvis: the obturator, hypogastric, external iliac and presacral nodes. The TNM system recognizes 4 different stages of LN involvement based on anatomic location rather than the size or number of lymph nodes. Metastasis in a single regional lymph node is classified as N1 stage, whilst involvement of > 1 regional node represents N2 disease. Metastasis in common iliac nodes is defined as N3 stage whilst spread to distant non-regional nodes i.e. at the level of aortic bifurcation or higher is considered metastatic disease and thus classified as M1a stage. Mapping studies have shown that there tends to be a step-wise ascending route of nodal spread with skipped stations above the aortic bifurcation being extremely rare (72, 76). In addition, primary lymphatic landing sites vary by the location of the bladder tumour with superolateral carcinomas having a tendency to spread first to external iliac LNs, whereas anterior wall, the base and trigone or bladder neck carcinomas primarily metastasizing to the internal iliac LNs (77). Although the primary tumour may be limited to one side of the bladder wall, bilateral LN involvement occurs in up to 40% (78). The standard bladder MRI protocol, which is primarily aimed at evaluating local T-stage, should ideally incorporate an additional sequence for the purpose of pelvic nodal staging from at least the level of aortic bifurcation. The knowledge of potential lymph node involvement above the common iliac bifurcation will direct treatment towards extended or super-extended lymphadenectomy, wherein nodal tissue up to the level of the aortic bifurcation or the inferior mesenteric origin is removed, respectively (79). MRI assessment for nodal metastases relies on size (>8 mm in short axis) and morphological criteria. Features of lymph node involvement include a rounded shape (reviewed on ≥2 perpendicular planes to avoid false positives), an irregular border, loss of fat in the hilum (normal nodes show T1 high signal intensity fatty hilum and loss of signal on DWI due to fat-saturation). Additional features may include similar T1 and T2 signal characteristics as that of primary tumour and/or central necrosis demonstrated by high T2 signal intensity and low T1 signal intensity with peripheral enhancement on DCE. However, MRI has limited accuracy in nodal assessment. A recent meta-analysis showed the pooled specificity on a per-patient basis to be high at 0.94, however, the pooled sensitivity is only 0.56 (18). Similarly, Salminen et al. reported a sensitivity range of 40.7-86% and specificity 31-92% (5/6 studies reported a specificity above 80%) (80). Size criteria alone will lack accuracy due to the inability to detect nodes involved with micrometastases, and over 90% of normal-sized metastatic LNs in BC have been shown to have a short axis diameter ≤ 5 mm (81). Conversely, false positive results are found in nodes enlarged due to reactive hyperplasia (82). Functional imaging of nodes has potential to overcome the limitations of morphological assessment alone (81, 83). ADC has been widely investigated as a biomarker for discriminating benign from malignant primary lesions in several tumour types and has shown potential to differentiate normal from metastatic nodes in BC (84). However, the relatively small size of nodes in relation to slice thickness of DWI means that derived ADC values can be significantly affected by partial volume effect and reproducibility is further limited by differences in acquisition protocols (e.g. vendor, field strength, b-value selection) (85, 86). Furthermore, a number of benign conditions including inflammation, sarcoidosis, lipomatosis, and follicular hyperplasia are known to cause restricted diffusion, leading to false positive results (81, 87–89). Thus, quantitative ADC values for assessment of involvement cannot be reliably applied. However, nodes display high signal on high b-value imaging due to an inherent long T2 relaxation time, meaning DWI can be used as a "nodal map" to identify nodal groups prior to correlation with anatomical imaging to limit false positive calls (bowel mucosa, nerves and vessels) (90) (Figure 11). Recent studies using this nodal mapping technique have reported improved sensitivities between 55-73% and specificities of 86-90% (81, 83). The most encouraging results in determining metastatic bladder nodes has been reported using MR lymphangiography (MRL) with ultra-small superparamagnetic iron oxide (USPIO) (91–93). This approach is however complex as it requires expertise, prolonged reading time and intravenous administration of USPIO 24-36h prior to scanning in order to allow time for nanoparticles to be taken up by macrophages which are abundant in benign lymph nodes but are replaced by malignant cells in metastatic LNs (92, 94). Accumulation of iron oxide causes loss of signal in normal LNs on post-contrast T2WI, T2W* imaging as well as on DWI, whereas involved LNs retain their high signal intensity and can thus be easily depicted. Meta-analysis by Woo et al. reported significantly improved pooled sensitivity at 0.86 when using MRL compared to a conventional approach (18). Unfortunately, USPIO is currently not licensed for routine clinical use and is limited for research purposes in prostate cancer alone (commercially known as Combidex) (94). In summary, lymph nodes should be identified on high b-value DWI, then further assessed on anatomical sequences for size (> 8mm), signal characteristics resembling the primary tumour and morphological criteria including rounded shape, an irregular contour and loss of fatty hila. However, given the limited sensitivity of MRI in detecting metastatic LNs in BC, negative MRI cannot obviate the need for lymphadenectomy if clinically indicated. Conversely, given the high specificity, suspicious nodes on MRI warrant a resection which should be extended when abnormal nodes are identified beyond the expected pelvic stations. MRI Urography and M-staging MRI Urography EAU guidelines recommend evaluation of the upper tracts in all patients with MIBC and in high-risk NMIBC cases (multiple or high-grade tumours and tumours located at the trigone) due to the high incidence of synchronous tumours of the upper urinary system (6). Although CTU is currently the modality of choice, use of MRU is recommended when there are contraindications for CTU (6) or in patients who need repeated imaging, due to the lack of ionizing radiation. However, there are no current guidelines on the optimal MRU protocol and the relatively long examination time and need for expert interpretation have limited its more widespread use. A typical MRU protocol combines static-fluid urographic imaging performed using T2-weighted sequences and excretory imaging performed using gadolinium-enhanced T1-weighted sequences in addition to morphological (T1W and T2W) renal imaging (19, 95). Premedication with a diuretic such as furosemide is generally recommended to achieve distention of the collecting systems and ureters and allow better visualization (19, 95, 96). Using only static-fluid technique which relies on intrinsically high signal intensity of urine for image contrast is preferred in pediatric population and in pregnant women as well as in patients with renal impairment (96). In addition, we also find it useful in the context of high risk BC patients as part of an all-in-one assessment of the urinary tract. We typically use coronal plane with a heavily-T2W technique, essentially the same as for MR cholangiopancreatography. MRU is a powerful diagnostic tool in depicting hydronephrosis and defining the level of obstruction (95) (Figure 12) with ureteric tumours presenting with intermediate T2 signal and corresponding restricted diffusion. M-staging At initial presentation, 10 - 15% of patients have metastatic disease, the commonest sites being lymph nodes, lungs, liver and bones (97). Furthermore, 50% of patients undergoing radical cystectomy will eventually progress either locally (30%) or with distant metastases (70%) (98). In patients with MIBC, contrast-enhanced CT of the chest, abdomen and pelvis remains the recommended imaging modality for assessment of nodal status and distant metastases. Bone scintigraphy (BS) is often used for bone assessment, particularly in symptomatic patients (6, 97). Despite several studies demonstrating MRI to have a superior sensitivity and specificity for detecting bone metastases (99–101) it has not been incorporated into current guidelines due to its limited availability, lack of expert knowledge and lower cost effectiveness. However, MRI can be especially beneficial in detecting early infiltration of bone marrow or for characterization of incidental detected indeterminate lesions on BS or CT (97, 101). In addition, partial M-staging of the bony pelvis and other pelvic structures is afforded by bladder mpMRI studies. Bone metastases in BC can be either lytic or sclerotic (102), and will exhibit low signal (SI) on T1W imaging, intermediate to low SI on T2W and will demonstrate restricted diffusion (high SI on DWI and low on ADC). High b-value DWI is particularly useful to depict high-signal intensity regions in bones which should subsequently be correlated with ADC and morphological sequences to avoid pitfalls (Figure 11). In addition, a proportion of BC patients are smokers or have chronic heart failure - conditions which tend to increase the cellularity of bone marrow (101). This may result in high SI on b-value DWI leading to false-positive calls, and potentially also false-negative findings, by obscuring metastatic infiltration of bone marrow (34). A study by Takeuchi et al. including 157 BC patients reported that only 27% of high signal intensity regions on DWI related to metastases, with the majority of false-positive findings relating to hematopoietic red marrow (103). Treatment response Assessing treatment response is of utmost clinical importance in that it can help determine candidates for bladder-sparing approaches in MIBC after neoadjuvant chemoradiation who show complete response (104) and for informing prognosis after neoadjuvant chemotherapy (NAC) followed by radical cystectomy, as patients with residual disease after NAC show worse survival (105). In addition, if non-responders can be predicted in advance, significant chemotherapy-related toxicities such as leukopenia can be avoided in these select patients (106). There has is accumulating evidence from experimental animal studies and early human studies that MRI has potential to play a pivotal role in this area with its advantages of avoiding exposure to ionizing radiation and multiparametric approach utilizing anatomical and functional sequences (e.g. DWI and DCE MRI) (12, 107–109). For example, Mazurchuk et al (109) demonstrated using orthotopic murine xenograft models of human bladder urothelial carcinomas that longitudinal MRI measurements were able to construct tumor growth curves and accurately measure reduction in tumor volume compared to necropsy specimens, providing a basis for MRI to be used in assessment/prediction of treatment response. Pretreatment MRI for prediction of treatment response Literature is sparse when it comes to the value of pretreatment MRI for predicting treatment response (Table 5). In a retrospective study by Yoshida et al (110), DWI was used to predict pathologic complete response (pCR) in 23 patients with MIBC undergoing cisplatin-based low dose chemoradiotherapy followed by partial or radical cystectomy. Using a cutoff of apparent diffusion coefficient values <0.74 x 10-3 mm2/s yielded sensitivity and specificity of 92% and 90%, respectively. In addition, in a study by Nguyen et al (111), DWI was used to predict response which was defined as either downstaging (to ypT1 or ypT2 with RECIST response) in a cohort of 20 patients with MIBC receiving cisplatin-based NAC followed by radical cystectomy. Patients with tumors resistant to NAC demonstrated higher entropy and lower uniformity on ADC maps, or in other words, showed a more heterogeneous spatial distribution of ADC values within the tumor compared with those that were sensitive. Overall, due to limited evidence there is currently no recommended imaging modality to predict NAC response (112). Interim MRI for prediction of treatment response MRI performed in the setting of interim evaluation of tumor response after the first few cycles of chemotherapy is potentially very useful, as earlier prediction of treatment failure can help decide to stop treatment to reduce unnecessary morbidity and costs (Table 5). In an early prospective study of MIBC or node-positive bladder cancer by Barentz et al (113), DCE was shown to be superior to anatomical sequences (T1-weigthed imaging) in predicting response during MVAC regimen (after the 4th cycle out of a total of 6 cycles), showing sensitivity and specificity of 93% and 100% for DCE-MRI and 79% and 63% for T1WI, respectively. Following studies by several investigators also demonstrated that DCE-MRI using various criteria (eg, relative signal intensity, size reduction, or K-means clustering) at mid-cycle of cisplatin-based chemotherapy in patients with MIBC or node-positive disease was useful in predicting responders with sensitivities and specificities of 83-96% and 83-100% (16, 114, 115). Assessment of treatment response after therapy Few studies have evaluated the role of MRI after completion of cisplatin-based chemotherapy or chemoradiation (Table 5). Choueiri et al (116) found that DCE-MRI after completion of treatment in patients with MIBC who received chemotherapy showed sensitivity and specificity of 79% and 55%, respectively, for determining responders. In addition, MRI-based response was predictive of superior 1-year disease-free survival rates: radiological responders, 86% (95% confidence interval, 63-95) vs non-responders, 62% (95% confidence interval, 31-82%). In addition, Donaldson et al (35) showed that DCE-MRI was able to detect residual tumor after chemotherapy with a sensitivity and specificity of 70% and 100%, respectively. It has also been observed that DWI (92%) is superior to DCE-MRI or T2-weighted imaging (18% and 45%, respectively) in terms of specificity for detecting residual tumor after chemoradiation in patients with MIBC albeit similar sensitivities (43-57%). Limitation and further directions Despite above promising results, several limitations should be noted regarding the use of MRI in assessing and predicting treatment response in bladder cancer. First, the published literature is this area is still small with most studies based on small number of patients (N = 12-40). Second, not only were the patient populations different (mostly MIBC, but some studies also including node-positive disease or distant metastasis), the definitions of response were quite heterogeneous among the studies (i.e., pCR, downgrading, or tumor size reduction). Third, methodology in assessing MRI response, including the type of MRI sequence (DCE-MRI, DWI, or T1-/T2-weighted imaging) and interpretation criteria (i.e., relative SI, tumor size, or histogram analysis) used were not uniform. Such heterogeneity should be resolved and methods tested by previous investigators should be validated in order for MRI to be used in clinical trials or even routine clinical practice. Radiomics Radiomics analysis of medical images has developed exponentially over the past decade, in particular in the field of oncological imaging, including for bladder cancer (32, 117–120). Radiomics can be performed on either anatomical and functional mpMRI sequences. Radiomic analyses of bladder mpMRI have shown promising results not only in estimating tumour grade and disease aggressiveness but also in predicting the local stage of BC (32, 117–119). Several quantitative features have been identified on T2WI which have proven useful in predicting both muscle invasive disease (117) and extravesical extension (119). A recent study by Xu et al. reported good performance (AUC = 0.861) in the preoperative prediction of muscular invasiveness by utilizing 13 T2WI radiomic signatures in 68 patients with clinicopathologically confirmed BC (117). Another study by Tong et al. included 65 patients undergoing radical cystectomy and identified 9 features which predicted T3 disease at a patient level with a sensitivity, specificity and AUC at 0.742, 0.824 and 0.806, respectively (119). Despite this early promise, further radiomic studies including DWI and DCE analysis and larger, multi-center datasets are required before radiomics can be employed in routine clinical practice to support and enhance local staging of BC and help optimize therapeutic management. Conclusion Accurate staging of BC is essential for determining both prognosis and optimal treatment. Current clinical staging lacks accuracy, whereas bladder mpMRI has shown high diagnostic performance in determining the local stage of BC and has the additional advantage of assessing tumour spread to lymph nodes, bones and involvement of the upper urinary tract. MRI also shows promise for predicting tumor aggressiveness and detecting therapeutic response to chemotherapy or radiotherapy and thus could be used to guide radical intervention and treatment of recurrence. References 1. 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Sample Bladder MR Imaging protocol according to VI-RADS Recommendations (1.5T and 3T) Technical parameters at 1.5T Technical parameters at 3T T2WI (axial, coronal and sagittal planes) FOV: 23 cm to encompass the entire bladder and surrounding structures TR/TE: 5000 ms/80 ms TR/TE: 4690 ms/119 ms Matrix: 256 x 189-256 Matrix: 400 x 256-320 Section thickens, gap: 4 mm, 0-0.4 mm Section thickens, gap: 3-4 mm, 0-0.4 mm Number of excitations: 1-2 Number of excitations: 2-3 DW Imaging: Axial plane (same orientation as for T2WI) Free-breathing spin echo EPI sequence combined with spectral fat saturation recommended FOV: 27 - 32 cm Section thickness, gap: 4 mm, 0-.0.4 mm Section thickness, gap: 3-4 mm, 0.3-0.4 mm TR/TE: 4500 ms/88 ms 
 TR/TE: 2500-5300 ms/61 ms 
 Matrix: 128 x 109 Matrix: 128 x 128 B values: 0-800 or 1000 s/mm2 B values: 0-800 or up to 2000 s/mm2 Number of excitations: 10-15 Number of excitations: 4-10 DCE: Axial plane (same orientation as for T2WI) 2D or 3D T1 GRE sequence; 3D is preferred; Fat suppression may be used 
 FOV: 27 - 35 cm Section thickness, gap: 2 mm, 0 mm Section thickness, gap: 1 mm, 0 mm TR/TE: 3.3 ms/1.2 ms 
 TR/TE: 3.8 ms/1.2 ms 
 Matrix: 256 x 214 Matrix: 192 x 192 Number of excitations: 1 Number of excitations: 1 Injection rate: 1.5-2 ml/s Temporal resolution: 30s 
 Total observation: >2min30s Adapted from reference [7]. FOV, field of view; EPI, echo planar imaging; DCE, dynamic contrast enhancement; 2D, two- dimensional; 3D, three-dimensional; TR, repetition time, TE, echo time; T2WI, T2-weighted imaging; GRE, gradient echo. 2 Table 2. Signal characteristics on multiparametric MRI Structure T1W T2W DWI DCEI (early)* DCEI (late)* Urine Low SI High SI No SI No SI High SI Muscle Intermediate SI Low SI Mildly increased SI Hypo enhancing Enhancing Tumour Intermediate SI Intermediate SI High SI Hyper enhancing Iso enhancing Perivesical fat High SI High SI No SI No SI No SI T2 stage Iso intense -> do no use for staging Low SI of muscle interrupted High SI partly within the muscle wall Disrupted low SI line with early enhancement Iso intense -> do not use for staging T3 stage High SI of fat interrupted High SI of fat interrupted High SI partly within the fat Disrupted low SI fat with early enhancement Disrupted low SI fat with enhancement T1WI = T1-weighted imaging; T2W = T2-weighted imaging; DWI = diffusion weighted imaging; DCEI = Dynamic contract enhanced imaging; SI = Signal *DCEI with fat suppression Table 3. VI-RADS scoring systems Score criteria T2W - Structural category 1 Intact muscularis propria with uninterrupted low SI line (Lesion < 1 cm; papillary tumour with or without stalk and/or thickened mucosa) 2 Intact muscularis propria with uninterrupted low SI line (Lesion > 1 cm; papillary tumour with stalk or sessile tumour and/or high SI of the thickened mucosa) 3 Lack of category 2 findings; either papillary tumour without stalk or sessile tumour without high SI thickened mucosa but no obvious disruption of low SI muscularis propria 4 Intermediate tumour SI interrupting the baseline low SI of muscularis propria 5 Intermediate tumour SI extending into extravesical fat DWI 1 Intact intermediate SI of the muscularis propria (Lesion < 1 cm; high SI on DWI and low on ADC, with or without stalk and/or thickened mucosa with low DWI SI) 2 Intact intermediate SI of the muscularis propria (Lesion > 1cm; high SI on DWI and low on ADC, with low DWI SI stalk or sessile tumour with thickened mucosa of low/intermediate DWI SI) 3 Lack of category 2 findings but no obvious high DWI SI disrupting the muscularis propria 4 High DWI and low ADC signal of the tumour focally disrupting the muscularis propria 5 High DWI and low ADC signal of the tumour extending into the perivesical fat DCE 1 No early enhancement of the muscularis propria 2 Early enhancement of the mucosa but not of the muscularis propria 3 Lack of category 2 findings but no obvious early enhancement of the muscularis propria 4 Focal extension of tumour early enhancement into the muscularis propria 5 Extension of tumour early enhancement into the perivesical fat Adapted from reference [7]. VI-RADS, Vesical Imaging-Reporting and Data System); T2W, T2-weighted imaging; DWI, Diffusion weighted imaging; DCEI, Dynamic contrast enhanced imaging Table 4. Assignment of overall VI-RADS score T2W score DWI score DCE score VI-RADS score 1 1 1 1 2 2 2 2 3 3 3 3 4 4 4 4 5 5 5 5 4 4 4 VI-RADS scoring summary: for categories 1–3, T2WI should be considered as the "first pass scoring". For scores 4 and 5, the dominant sequences are DWI (first) and DCEI (second). VI-RADS, Vesical Imaging-Reporting and Data System); T2W, T2-weighted imaging; DWI, Diffusion weighted imaging; DCEI, Dynamic contrast enhanced imaging Table 5. Summary of the main studies investigating treatment response First author Cohort details Definition of response MRI details Endpoint Conclusion No. of patients Tumor Treatment Reference standard Response criteria Response rate Tesla Sequence Response assessment criteria Pretreatment Yoshida S, 2011 23 MIBC (T2-3aN0M0) CRT (4 wks RT + 2 cycles of cisplatin on 1/4th wks) RC or PC pCR 13/23 1.5 DWI (ADC) ADC < 0.74 x 10-3mm2/s CRT-sensitive tumors sens/spec 92/90 Nguyen HT, 2017 20 MIBC pT2 GC or MVAC 4 cycles RC ypT1 or pT2 with RECIST response 15/20 3 DWI (ADC) not available not available resistant cases had higher entropy, lower uniformity(P<0.01,=0.01) Interim Barentsz JO, 1998 22 "advanced" BC, T1-4b, N1(n=18) or M1(n=1) MVAC 6 cycles cystectomy or TUR no or "few"(<5% of resected specimen) microscopic areas of viable tumor 14/22 1.5 DCE, conv (unenhanced T1 and T2) tumor or LN; 50% size reduction in two dimensions; or earliest enhancing region changes to >10s after main artery in same plane responder DCE 93/100; conv 79/63 Schrier BP, 2006 36 MIBC (>=T2, N1-2); regionally met or unresectable MVAC 6 cycles cystectomy or TUR no or "few" microscopic areas of viable tumor 22/36 NR DCE, conv (unenhanced - Anatomical imaging - not defined) tumor or LN; responder if >50% decrease in summed products of longest perpendicular D of all lesions with no simultaneous increase in size or new lesion; CE changed to >10s responder DCE sens/spec 91/93; conv 81/50 Chakiba C, 2015 12 MIBC (T2N0M0) GC, MVAC, or HD-MVAC 3-6 cycles cystectomy or TUR absence of infiltrative tumor in sample 6/12 1.5 DCE rSI80 (relative SI at 80 sec after injection normalized to unenhanced image)>40% ? 83.33/83.33 Nguyen HT, 2014 30 not available Cisplatin-based chemotherapy RC pCR, downstaging, or >50% tumor volume reduction w/o stage change 23/30 3 DCE k-means clustering responder 96/100 Posttreatment Choueiri TK, 2014 39 cT2-cT4, N0-1, M0 ddMVAC RC pathologic downstaging to ≤pT1pN0 19/39 NR DCE >50% decrease in the product of the longest perpendicular diameters and delayed enhancement of residual tumor responder sens/spec 78.9/55.0 Donaldson SB, 2013 21 MIBC GC 3 cycles cystectomy "residual" 14/24 1.5 DCE two different DCE variables_rSI80>2.6 ; Fp>19.0 residual tumor 70/100 and 60/86 Yoshida S, 2010 20 MIBC (T2-4aN0M0) CRT (4 wks RT + 2 cycles of cisplatin on 1/4th wks) RC or PC pCR 13/20 1.5 T2/DCE/DWI T2WI bladder wall thickening; DCE early intense enhancement; DWI high SI on b-value both 500 and 1000 residual DWI 57/92; T2 43/45; DCE 57/18 Supplemental table 1. TNM (8th Edn.) Guidelines for the Staging of Bladder Cancer T - Primary Tumor TX Primary tumour cannot be assessed T0 No evidence of primary tumour Ta Non-invasive papillary carcinoma Tis Carcinoma in-situ T1 Tumour invades subepithelial connective tissue T2 Tumour invades muscle layer T2a Tumour invades inner half of the muscle T2b Tumour invades outer half of the muscle T3 Tumour extends into perivesical tissue T3a Microscopically T3b Macroscopically (extravesical mass) T4 Tumor invades adjacent structures T4a Tumour invades prostate, seminal vesicles, uterus or vagina T4b Tumour invades pelvic wall or abdominal wall N - Regional Lymph nodes NX Regional lymph nodes cannot be assessed N0 No positive regional lymph nodes N1 Metastasis in a single lymph node in the true pelvisa N2 Metastasis in multiple regional lymph nodes in the true pelvisa N3 Metastasis in common illiac lymph node(s) M - Metastasis M0 No distant metastasis M1a Nonregional lymph node(s) M1b Distant metastasis to other sites Adapted from: Reference [7] a hypogastric, obturator, external illiac or presacral lymph node station Figure Legends Figure 1. Tumour within bladder diverticulum. Axial T2-weighted imaging (A) and diffusion weighted imaging (B) demonstrate a lesion (arrow) in bladder diverticulum. It exhibits intermediate T2 signal, has restricted diffusion and measures <1 cm, but the extent of tumour is unlikely tobe appreciated on cystoscopy alone. The lack of a true muscle layer in diverticula mean there is no T2-stage, and in this case tumour is clearly extending into the perivesicular fat in keeping with stage T3b. Figure 2. Higher spatial resolution of T2-weighted imaging helps determine depth of invasion. Multifocal bladder tumours arising from the left lateral bladder wall. The most posterior tumour (arrow) shows intermediate signal with clear extension into the low signal muscularis propria on T2-weighted imaging (inset) in keeping with T2b disease whereas the tumour above it (inset) invades only the inner half of the muscular layer (T2a disease). Both tumours more anteriorly are confined to the mucosa. B: Diffusion weighted imaging (DWI) shows corresponding high signal but the depth of invasion is more challenging to define in such small lesions due to limited spatial resolution. Conversely, DWI readily depicts a small tumour arising from the right lateral wall which could be mistaken for a mucosal fold on T2Wi alone (arrow head). Figure 3. Susceptibility weighted artefacts. A: T2-weighted imaging (T2WI) demonstrates air within the sigmoid colon which is causing significant warping and signal loss on diffusion weighted imaging (DWI, arrows) (B). Post-cystoscopy non-dependent air within the bladder seen as an area with no signal beneath the anterior bladder wall on T2WI (C) with significant distortion of the bladder in the corresponding region on DWI (D, arrows). Figure 4. Suboptimal bladder filling. A: Under-distended bladder on sagittal T2-weighted imaging. Collapsed mucosa may mimic tumour (arrow) whereas wall folding may compromise detection of small lesions. B: Over-distended bladder. Bladder wall spasm and/or patient motion resulting in motion artefacts as shown on sagittal T2-weighted imaging. In addition, thinning of the wall decreases sensitivity for flat lesions. Figure 5. VI-RADS score 2. 76-year-old female presenting with haematuria and bladder lesion identified on ultrasound. T2-weighted imaging (A: axial plane) shows an exophytic lesion on the lower anterior bladder wall, > 1 cm in greatest dimension, with preserved low SI of the muscularis propria (VI-RADS score 2). B: Diffusion weighted imaging (DWI) with b-value = 2000 and ADC map (C), respectively, demonstrates an exophytic lesion with restricted diffusion, with low signal stalk on DWI (arrow) and muscularis propria with continuous low signal on DWI (VI-RADS score 2). D: Dynamic contrast enhanced (DCE) imaging shows early enhancement of the lesion and inner layer, without early enhancement of the muscularis propria (VI-RADS category 2). Overall VI-RADS score 2 was assigned and pT1 urothelial carcinoma was confirmed at histopathology after trans urethral resection of bladder tumour (TURBT). Figure 6. VI-RADS score 5. 65-year-old male with haematuria and positive cytology. A: T2-weighted imaging demonstrates a lesion >1 cm in the left lateral bladder wall, with intermediate signal that extends through the muscularis propria and to the origin of the left seminal vesicle (VI-RADS score 5) with corresponding significant restricted diffusion on DWI (B: b-value = 2000) and on ADC map (C); VI-RADS score 5. D: There is early and heterogeneous enhancement of the lesion, which extends through the muscularis propria on dynamic contrast enhanced imaging (VI-RADS category 4). Overall VI-RADS score 5 was assigned. Muscle involvement was proven at histopathology after trans urethral resection of bladder tumour. Figure 7. T2 versus T3 stage. A, B: 82-year-old man with T2 stage tumour. A: T2-weighted imaging (T2WI) shows left posterolateral bladder mass with irregular border and decreased signal of the perivesicular fat (arrow). B: Diffusion weighted imaging (DWI) shows a smooth outer outline with no increased signal within the perivesicular fat (arrow) thus confirming T2 stage. C, D: 68-years-old male with T3 stage tumour. A: There is a left-sided posterolateral bladder mass with an irregular border and decreased signal of the perivesicular fat on T2WI (arrow). B: DWI shows an irregular outer outline of the tumour with high signal extending into the perivesicular fat (arrow), thus confirming extravesicular extension. Figure 8. T4a stage with prostate invasion. 78-year-old man with macroscopic haematuria and urinary retention. A: Sagittal T2W image shows diffuse bladder wall thickening with intermediate SI extending inferiorly and involving most of the prostate (arrows). B: Axial T2W image at the level of the prostate demonstrates tumour infiltration of the gland with corresponding restricted diffusion on ADC map (C). Note urinary catheter on sagittal image (A). Figure 9. T4b stage with pelvic sidewall invasion. 52-year-old man with advanced disease. A: Axial T2-weighted imaging (T2WI) shows abnormal bladder wall thickening with intermediate to low signal tumour extending to the left pelvic sidewall (arrows) and mesorectal fat. B, C: Axial diffusion weighted imaging and ADC map show associated restricted diffusion. Note two filling defects on T2WI within two bladder diverticuli consistent with tumours (A, *) with corresponding restricted diffusion (B, C). Figure 10. Post-procedural inflammation. There is diffuse bladder wall thickening with intermediate to high signal on T2-weighted imaging (A) and corresponding high signal on diffusion weighted imaging (B). The features could be mistaken for residual diffuse infiltrative tumour, however, high signal on ADC map (C) confirms no restricted diffusion and T2-shine-through effect. Note focal procedure-related perforation anteriorly (arrow) with a small amount of free perivesicular fluid. Figure 11. Nodal and bone metastases. 57-year-old man with metastatic bladder cancer. A, B: Axial T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) show enlarged left pelvic sidewall lymph nodes and low to intermediate signal bone metastases in the sacrum (arrows); more conspicuous as high signal on b-value diffusion weighted imaging (DWI) (C). Note the most right bone lesion is hardly seen on T1WI and T2WI. Figure 12. Synchronous ureteric malignancy in a patient with high risk bladder carcinoma. MR cholangiopancreatography-like heavily-T2-weighted sequence in coronal plane readily demonstrates duplex right kidney (proximal union of the ureters) with severe dilatation of both moieties and severe dilatation of the common right ureter due to obstructing distal ureteric tumour. Normal left collecting system and ureter. Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. Figure 8. Figure 9. Figure 10. Figure 11. Figure 12. image1.png image2.png image3.png image4.png image5.png image6.png image7.png image8.png image9.png image10.png image11.png image12.png