Keywords

Introduction

Cystoscopy with transurethral bladder tumor resection is the primary diagnostic direct visualization technique for the initial diagnosis of bladder cancer [1, 2]. Since the most common presentation of bladder cancer is hematuria, cystoscopy is recommended by the American Urological Association for bladder evaluation, and therefore, the role of diagnostic imaging is limited in the initial diagnosis [1, 2]. However, imaging of bladder cancer is critical for local and distant staging, detection for metachronous and synchronous upper tract urothelial carcinoma, assessment of treatment response, evaluation of disease, and treatment-related complications [1,2,3,4].

Additionally, recently proposed multiparametric MRI staging of bladder cancer may also be used to identify muscle-invasive disease, although the specific clinical role of this technique has not been established yet [5]. Furthermore, newly developing radiomics techniques may also have a role in the imaging evaluation of bladder cancer [6].

Role of Imaging in the Diagnosis of Bladder Cancer and Directing the Therapeutic Approach

The initial diagnosis of bladder cancer is usually made during hematuria workup. According to the American Urological Association, in patients with gross or visible hematuria and high-risk microscopic hematuria, in addition to cystoscopy, assessment of the upper tract is performed by cross-sectional urographic imaging techniques including CT and MR urography [1]. The use of renal ultrasound is recommended in patients with intermediate-risk microscopic hematuria in addition to cystoscopy [1]. Repeat urine analysis in 6 months versus cystoscopy and renal ultrasound is recommended for the patients with low-risk microscopic hematuria [1].

Upper tract imaging with CT and MR urography is performed since synchronous urothelial carcinoma is seen in 2% of the patients with bladder urothelial carcinoma, and metachronous urothelial carcinoma is seen in 3.9% of the patients with history of bladder cancer [3]. CT urography is the most commonly used technique for imaging of upper tract [1, 2, 7]. However, if there is history of severe allergy or anaphylaxis to iodinated contrast media, MR urography could be performed with gadolinium-based contrast media [8]. If there is history of moderate allergic reactions to IV contrast agents, preprocedural preparation of patients is recommended with the use of steroid regimens [9]. If the patient is on dialysis without concern for any residual renal function, CT including precontrast and postcontrast imaging could be performed although the assessment could be limited due to the lack of excretory phase secondary to poor renal function [10]. MRI with contrast should not be preferred in patients undergoing dialysis or acute renal failure, and stable agents should cautiously be used in patients with stage 4 and 5 chronic kidney disease [11]. Alternative imaging techniques including renal ultrasound or noncontrast MRI also employing noncontrast urography techniques could be performed if CT or MR could not be performed due to pregnancy, history of severe allergic reactions, anaphylaxis, renal impairment, or the presence of incompatible implants with MR imaging or implants impairing image quality on CT and MRI [1, 2, 8, 10, 11]. The details of alternative imaging approaches are summarized in Table 5.1. A retrograde pyelogram could also be performed if the findings on imaging are inconclusive [1, 2].

Table 5.1 Alternative imaging approaches when contraindications and relative contraindications to specific imaging modalities are present
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Besides the detection of upper tract disease, cross-sectional imaging with CT and MRI is also used for local and distant staging [12,13,14]. Histopathologic staging is performed with the TNM system published as the 8th edition of the American Joint Committee on Cancer in 2018 [15]. Urothelial carcinoma is the most common type of bladder cancer forming 90% of the bladder cancers in the Western world [2, 3, 13, 14]. Squamous cell carcinomas and adenocarcinomas forming 6–8% and 2% of the bladder cancers are rare in the Western world [2, 3, 13, 14]. Squamous cell bladder cancer is the major type seen in developing countries where schistosomiasis is endemic [2, 14]. Squamous cell carcinomas and adenocarcinomas are aggressive tumors and usually present with advanced disease [14].

Cross-sectional imaging with CT and MRI is is used to assess the treatment response including tumor burden, lymph node involvement, and distant metastases following TURBT, chemotherapy, immunotherapy, and radiotherapy and surgery.

Surveillance with cross-sectional imaging following treatment of non-muscle-invasive bladder cancer is performed at every 1–2 years for the assessment of upper tract in patients with intermediate (including recurrence of low-grade Ta within 1 year, solitary low-grade Ta >3 cm, high-grade Ta ≤3 cm, and low-grade T1) and high (high-grade T1, recurrent high-grade Ta, high-grade Ta >3 cm or multifocal high-grade disease, carcinoma in situ, BCG failure in high-grade disease, lymphovascular invasion, high-grade prostatic urethral involvement) risk non-muscle-invasive disease [2]. For low-risk non-muscle-invasive disease, no routine upper tract imaging is recommended [2]. Surveillance with cross-sectional imaging for nonmetastatic muscle-invasive bladder cancer following cystectomy is performed with CT or MR urography and chest radiography or chest CT every 3–6 months for 1–2 years, CT/MR and chest radiography or chest CT annually for 3–5 years, and renal ultrasound for 5–10 years [2]. Surveillance with cross-sectional imaging for nonmetastatic muscle-invasive bladder cancer following bladder sparing treatment is performed with CT or MR urography and chest radiography or chest CT every 3–6 months for 1–2 years and CT/MR and chest radiography or chest CT annually for 3–5 years [2]. PET/CT with FDG could be performed for further assessment if metastatic disease is suspected during the surveillance [2]. There are no specific guidelines for the surveillance of metastatic muscle-invasive bladder cancer, although short-term follow-up with 3–6 month intervals is also preferred [2]. Contrast-enhanced studies are done for the abdomen and pelvis if there is no contraindication to IV contrast. If chest CT studies are done without concurrent CT studies for the abdomen and pelvis, IV contrast use is not necessary for the assessment of the chest.

Cross-sectional imaging with or without urography is also essential for the assessment of disease or treatment-related complications including but not limited to bladder rupture following TURBT, fistulization to the adjacent organs such as vagina or rectum, anastomotic leaks following urinary diversion or partial cystectomy, anastomotic strictures, and reflux from the conduit into the ureters and kidneys.

Imaging Modalities

Ultrasound

Imaging Technique

Bladder ultrasound is performed by using a 2–5 megahertz (MHz) convex probe [3]. In order to be able to assess the bladder wall and lumen, the bladder has to be distended at least moderately with urine or fluid. The bladder volume of 250–500 ml is usually sufficient for optimal bladder distention. If the bladder is not distended, US assessment will be extremely limited or nondiagnostic. About 500–1000 ml of fluid intake is encouraged 1 hour before the bladder US. In patients with indwelling urinary catheter, 250–500 ml saline is administered to the bladder through the catheter to provide bladder distension if the patient is able to tolerate. Color Doppler US technique is also used to detect vascularity in suspicious bladder lesions [3]. Reverberation artifacts, side lobe artifacts, section thickness artifacts, and range ambiguity artifacts may impair the image quality and adversely affect the detection of focal lesions during bladder US [16]. Reverberation artifacts and side lobe artifacts could be avoided by using tissue harmonic imaging, changing the angle of insonation, and decreasing gain [16]. Section thickness artifacts can be avoided by placing the area of interest in the focal zone [16]. Range ambiguity artifacts can be avoided by reducing the number of focal zones and increasing the image depth [16].

Imaging Role, Clinical Impact, and Accuracy of US

Bladder cancer can be incidentally detected during evaluation for other reasons including but not limited to lower urinary tract symptoms, infection, and urinary retention. Bladder ultrasound is also done to assess the presence and size of potential intraluminal bladder hematoma secondary to hematuria.

Bladder cancer can present as diffuse bladder wall thickening, focal bladder wall thickening, polypoid bladder mass, or sessile focal lesions along the bladder wall [3]. The lesions may demonstrate variable echogenicity and usually irregular contours [3]. Calcifications could be seen in the lesions. Hematomas could potentially be differentiated from bladder cancer with the help of mobility during the real-time ultrasound examination. Hematomas usually demonstrate mobility with the movement of patients, while bladder cancer lesions are immobile. Vascularization could be detected in bladder cancer lesions with color Doppler. Muscle-invasive cancer can be diagnosed when the muscular hypoechoic middle layer of the bladder is involved with tumor. The normal inner mucosal and outer serosal layers of the bladder are seen as hyperechoic layers.

The detection and assessment of muscle involvement with staging of bladder cancer are limited due to low soft tissue contrast resolution , inadequate bladder distension, and operator dependence [3]. The sensitivity and specificity for the detection of bladder cancer with ultrasound are variable and have been reported to vary between 60.9% and 63% and 72.1% and 99%, respectively [3].

Computed Tomography

Imaging Technique

CT is the most commonly used technique for the assessment of bladder cancer including detection and staging [14]. CT urography is the preferred method for the evaluation of bladder cancer during the initial diagnosis and surveillance at least for 1–2 years due to the ability to assess locoregional disease, lymph nodes, distant metastasis, and potential upper tract disease [1, 2, 13, 14]. CT urography includes the noncontrast phase of the abdomen and nephrographic phase and excretory phase of the abdomen and pelvis (Fig. 5.1) [4, 7, 13, 17, 18]. The noncontrast phase is usually acquired for the abdomen only to decrease radiation exposure. However, virtual noncontrast series of the abdomen and pelvis could also be created without additional exposure to radiation if dual-energy CT techniques are used [7, 17]. The nephrographic phase is usually acquired at 70 seconds after contrast administration, and the excretory phase is usually acquired at 5–6 minutes after contrast administration [17]. Split bolus technique which is used at some institutions performs CT urography with the administration of contrast bolus at two different times. By split bolus technique, in addition to noncontrast phase, nephrographic and excretory phase images are acquired at the same time, which overall decreases radiation exposure and scanning time [7, 18]. However, it has been reported that the inability to assess the enhancement of the walls of the renal collecting system, renal pelvis, ureters, and bladder wall due to masking effect of excreted contrast limit the detection of small lesions [13]. Sample CT urography protocols are given in Table 5.2.

Fig. 5.1
figure 1

Normal CT urogram. Transverse noncontrast (a), transverse nephrographic phase (b), coronal nephrographic phase (c), transverse excretory phase (d), and coronal excretory phase (e, f) CT images showing a sample triphasic CT urogram acquired at 64-slice single energy CT scanner. Please note that intermediate window setting is preferred for the assessment of contrast-filled renal collecting system, ureters and bladder for the detection of focal lesions

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Table 5.2 CT urography technique
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Imaging Role, Clinical Impact, and Accuracy of CT

In diagnostic workup of suspected bladder cancer, CT urography is performed in combination with cystoscopy and transurethral bladder tumor resection (if there is any lesion) for the detection and staging of bladder cancer (Fig. 5.2) [1, 2]. Sensitivity, specificity, and accuracy of CT urography have been reported to be 79%, 94%, and 91% for the detection of bladder cancer [4, 13]. CT urography is particularly limited in the detection of small particularly flat and sessile lesions [14]. CT has overall low accuracy in T staging of bladder cancer, and it is especially limited to differentiate non-muscle-invasive and muscle-invasive disease if there is no obvious extravesical invasion. The sensitivity, specificity, and accuracy for the identification of T3 disease, i.e., bladder cancer with extravesical extension, vary between 62% and 89%, 63% and 100%, and 49% and 93% [3, 4, 13, 14].

Fig. 5.2
figure 2

Bladder cancer. Transverse (a) and coronal (b) CT images acquired at the nephrographic phase, and transverse (c) and coronal (d) CT images acquired at the excretory phase demonstrate a polypoid heterogeneously enhancing mass arising from the right posterolateral wall of the bladder and extending into the bladder lumen at the level of right ureterovesical junction. The mass is not obstructing since there is no obvious evidence of hydroureter or hydronephrosis. Please note the presence of calcifications at the periphery of the mass

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CT is also limited in the staging of lymph nodes since CT assessment relies only on the size and morphology of the lymph nodes. Lymph nodes with a short-axis size larger than 1 cm are regarded as abnormal lymph nodes , and those with 0.8 cm are usually regarded as suspicious lymph nodes in the pelvis and retroperitoneum. Additionally, round morphology is usually regarded as abnormal particularly if the lymph nodes are 0.8 cm and larger. Variable sensitivity, specificity, and accuracy have been reported for the detection of lymph node metastasis by CT ranging from 9% to 83%, 56% to 100%, and 54% to 86%, respectively [13].

CT urography is used for the identification of synchronous and metachronous upper tract urothelial carcinoma (Fig. 5.3) during the initial diagnostic workup and surveillance with sensitivity, specificity, and accuracy ranging between 93.5% and 95.8%, 94.8% and 100%, and 94.2% and 99.6% [19]. The positive predictive value of CT urography has also been reported to be 53% overall, 83% for large masses, 0% for small masses, and 46% for urothelial thickening [20].

Fig. 5.3
figure 3

Bilateral ureter masses. Transverse noncontrast (a), transverse (b), and coronal corticomedullary phase CT images show a right small enhancing ureter mass (arrows, a–c). Transverse noncontrast (d), transverse (e), and coronal (f) corticomedullary phase CT images show a left-sided larger enhancing ureter mass (arrows, d–f). The lesions are obstructive and associated with bilateral hydroureteronephrosis (not shown)

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CT urography is also able to assess distant metastatic disease including retroperitoneal lymph node and distant organ metastases in the abdomen and pelvis.

Magnetic Resonance Imaging

Imaging Technique

MRI of the bladder can be performed at 1.5 T or 3.0 T with phased-array body coils. No patient preparation is necessary for the examination unless the patient needs premedication due to prior history of moderate allergic reaction to gadolinium-based contrast media.

MR Urography

MR urography could be performed for the assessment of not only hematuria but also lower urinary tract symptoms , urinary obstruction (associated with bladder cancer), and synchronous and metachronous urothelial cancers [8, 12, 18, 21]. Additionally, MR urography can be used for surgical planning if there is additional complex history of prior surgeries or congenital anomalies [12]. IV administration of 250 ml of saline 15–30 minutes before the examination would be helpful to hydrate the patient [8, 12]. The patients are instructed to void just before the examination. MR urography sequences are performed following the IV administration of diuretic agent furosemide with the dose of 0.1 mg/kg or 5–10 mg for the adults if there is no contraindication to the diuretics [12]. The acquisition of MR urography sequences is performed on the coronal plane extending from the top of the kidneys to the level of the inferior border of the external urethral sphincter in the males and to the level of urethral meatus in the females. In addition to MR urography sequences, precontrast sequences including transverse and coronal T2-weighted single-shot echo train spin echo (SS-ETSE), transverse T2-weighted fat-suppressed SS-ETSE, transverse T1-weighted in-phase and out-of-phase gradient echo, transverse and coronal T1-weighted precontrast fat-suppressed gradient echo, and transverse diffusion weighted imaging sequences are acquired.

MR urography studies can be performed by using two urographic techniques including (i) fluid-based T2-weighted imaging and (ii) contrast media-based excretory phase imaging employing T1-weighted imaging (Fig. 5.4). Sample MR urography protocol at 1.5 T is given in Table 5.3.

Fig. 5.4
figure 4

MR urography. Coronal T2-weighted single shot echo train spin echo (SS-ETSE) (a), coronal T2-weighted thin slice fat-suppressed SS-ETSE (b), coronal T2-weighted thick-slab single shot turbo spin echo (c), coronal T1-weighted postgadolinium excretory phase three-dimensional gradient echo (3D GE) images demonstrate the compression of right ureter mildly due to right common iliac artery (thin arrows) on noncontrast fluid-based MR urography images (b, c) and postcontrast excretory phase MR urography (d) image. Ureteropelvic junction mass. Transverse T2-weighted SS-ETSE (e) and transverse T1-weighted fat-suppressed 3D GE (f) images demonstrate a left ureteropelvic junction mass (arrows, e, f)

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Table 5.3 MR urography technique at 1.5 T
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Fluid-based MR urography can be performed by using two-dimensional T2-weighted SS-ETSE sequences with thinner slices for the assessment of renal collecting systems particularly and single-shot thick slab heavily T2-weighted turbo spin echo (TSE) for the assessment of ureters particularly. The fluid-based MR urography technique is especially critical in pregnant patients since ionizing radiation and gadolinium-based contrast agents cannot be used.

Contrast-based MR urography is performed using three-dimensional gradient echo T1-weighted sequences following the IV administration of gadolinium-based contrast agents. Dynamic imaging is performed on the corticomedullary phase (35 seconds after the contrast administration), nephrographic phase (60–70 seconds after the contrast administration), and excretory phase (5–8 minutes after the contrast administration). Subtraction of precontrast series from postcontrast series could be particularly helpful for the creation of three-dimensional images. Additionally, transverse and sagittal fat-suppressed three-dimensional gradient echo sequences could also be obtained on the nephrographic and excretory phases.

Bladder Cancer Staging

MRI can also be used specifically for staging bladder cancer to differentiate muscle-invasive disease from non-muscle-invasive disease . The patient is instructed to void 60 minutes before the examination and given 500–1000 ml of fluid to drink 30–60 minutes before the examination to distend the bladder.

The key sequences for the staging of bladder cancer include high-resolution T2-weighted TSE sequence in three planes, diffusion weighted imaging (DWI)) and dynamic contrast-enhanced (DCE) postgadolinium three-dimensional gradient echo imaging of the bladder. These examinations should be performed with a small field of view, thinner slices (3–4 mm) without any intersection gap, and a high image matrix. DCE imaging is performed at the arterial phase, venous phase, interstitial phase, and excretory phase. Multiple repeated acquisitions through the bladder could be very helpful to assess the enhancement patterns of focal lesions during the arterial (25 seconds after the injection), venous (60 seconds after the injection), interstitial (120 seconds after the injection), and excretory phases (360 seconds after the injection).

In addition to these staging sequences, precontrast and postcontrast sequences for the assessment of the pelvis are also acquired . This is particularly important for the assessment of lymph node involvement, complications, and any additional chronic and incidental pathology or findings. A sample MRI protocol for bladder cancer staging is given in Table 5.4.

Table 5.4 MR technique for bladder cancer staging of pelvis at 1.5 T
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Imaging Role, Clinical Impact, and Accuracy of MR

MR Urography

MR urography is an accurate imaging technique for the detection of bladder cancer during the workup of hematuria or lower urinary tract symptoms, and the sensitivity of MR urography (91%) is similar to that of CT urography (94%) [21]. Although MR urography has been reported to be moderately sensitive for the detection of upper tract disease (Fig. 5.4), the literature is still scarce, and MR urography has been reported to have high sensitivity for the detection of upper tract disease and likely comparable to CT urography [18].

MR urography can be used in combination with MR angiography and standard MR imaging to assess the arterial supply of the kidneys , collecting system of the kidneys, ureters, renal parenchyma, and bladder in one examination for preoperative assessment. Additionally, MR urography can be used to assess postoperative complications following cystectomy or treatment of upper tract disease such as urinomas or urine leaks, fistulas involving the GU tract.

MR urography with noncontrast techniques can also be used in pregnant patients and in patients who are not able to get IV contrast due to renal impairment or allergic reactions.

Bladder Cancer Staging

Bladder cancer staging is performed by using T2-weighted high-resolution TSE sequences, DWI sequence and DCE sequence . The remaining sequences are used for the evaluation of lymph node involvement, possible distant metastases, and additional incidental findings.

T Staging

The muscularis propria is the predominant layer at the bladder wall and is hypointense on T2-weighted TSE, mildly hyperintense on high-value is the DWI showing intermediate signal intensity on ADC map, and hypointense on T1-weighted images. The mucosa and submucosa could not be differentiated on T2-weighted TSE and DWI images [5, 14, 22,23,24,25,26,27]. Early enhancement of the mucosa and submucosa on the arterial phase DCE images is visualized, while muscularis propria demonstrates late enhancement on the venous and interstitial phase DCE images [5, 14, 22].

Intermediate to low signal of the tumor on T2-weighted TSE images is seen compared to background hypointense muscularis propria and therefore could be differentiated from the normal bladder wall [5, 14, 22]. High DWI signal intensity of the tumor with corresponding low signal intensity on ADC compared to the muscularis propria [5, 14, 22] differentiates the tumor from the bladder wall. Prominent enhancement of the tumor compared to nonenhancing or minimally enhancing muscularis propria on the arterial phase of DCE imaging differentiates the tumor from the bladder wall [5, 14, 22].

These features help the recognition and staging of the tumor with differential signal compared to the underlying background bladder wall [5, 14, 22]. The extension of tumor into the muscularis propria and extravesical fat tissue differentiates T1 versus T2 and T2 versus T3, respectively [5, 14, 22].

A fibrotic and/or inflammatory stalk arising from the submucosa, with no evidence of malignancy, is usually associated with Ta and T1 tumors [5, 14, 22]. The stalk usually shows intermediate to low signal intensity on T2 TSE images although the signal can be variable [5, 14, 22]. Low signal on high b values images with associated high signal on ADC map without diffusion restriction is also seen at the stalk which also usually shows early enhancement on DCE similar to the tumor [5, 14, 22]. The tumor is usually a non-muscle-invasive tumor and the tumor signal does not extend to the muscularis propria when the stalk is present [5, 14, 22]. Additional findings which are suggestive of non-muscle-invasive tumor also include tenting of the bladder wall and uninterrupted submucosal enhancement just beneath the tumor [5, 14, 22]. The submucosa sometimes is seen as a thickened layer under the tumor and the absence of diffusion restriction would be suggestive of inflammation and /or fibrosis. However, the stalk may occasionally show diffusion restriction without evidence of malignancy, and T1 tumors may also invade the submucosa without the presence of stalk [5, 14, 22]. Additionally, if there is discordance between the findings of T2 TSE, DWI or DCE, DWI should be the dominant sequence in staging due to the potential to differentiate the tumor tissue from inflammation and/or fibrosis [14, 28].

When the tumor is confined to the bladder wall and the intermediate tumor signal does not extend through the dark signal of muscularis propria completely on T2-weighted TSE images, the tumor is T2 [5, 14, 22]. The tumor shows a high DWI signal with a corresponding low ADC signal, and increased arterial phase enhancement confined to the wall without any extension to perivesical fat [5, 14, 22]. However, if there is discordance between the findings of T2 TSE, DWI or DCE, DWI should be the dominant sequence in staging due to the potential to differentiate the tumor tissue from inflammation and/or fibrosis [5, 14, 22]. DWI should be the dominant sequence in staging due to the potential to differentiate the tumor tissue from inflammation and/or fibrosis when there is perivesical inflammation and fibrosis due to treatment or postprocedural changes which may demonstrate similar signal to the tumor on T2-weighted images or similar enhancement to the tumor on DCE [5, 14, 22].

A recently proposed system for the determination of muscle-invasive disease on MRI which is called Vesicle Imaging-Reporting and Data System (VI-RADS) has been reported to have high accuracy with sensitivity of 87–92% and specificity of 79–87% [5, 22, 24,25,26,27]. However, this system is at its early stages of development , and there are still very limited studies for the validation of this system in the literature. Therefore, more studies are needed to determine its specific role in the diagnostic algorithm. VI-RADS) also depends on the determination of tumor extension through the bladder wall on T2-weighted TSE, DWI and DCE sequences. If the tumor is less than 1 cm with no evidence of extension of intermediate soft tissue tumor signal on T2 TSE, a corresponding signal on DWI/ADC signal and early enhancement on DCE into the muscularis propria, VI-RADS category is 1, and the muscle invasion is highly unlikely [5, 22]. If the tumor is larger than 1 cm with no evidence of extension of intermediate soft tissue tumor signal on T2 TSE, corresponding signal on DWI /ADC signal and early enhancement on DCE into the muscularis propria, VI-RADS category is 2, and the muscle invasion is unlikely [5, 22]. If there is exophytic intraluminal tumor without stalk or sessile tumor without evidence of non-enhancing T2 high signal intensity inner lining and without disruption of muscularis propria, VI-RADS category is 3, and the muscle invasion is equivocal [5, 22]. If there is evidence of interruption of normal signal intensity of muscularis propria with tumor extension on T2 TSE with associated corresponding abnormal DWI/ADC signal and early enhancement on DCE, VI-RADS category is 4, and the muscle invasion is likely [5, 22]. If there is evidence of complete interruption of normal signal intensity of muscularis propria with tumor extension into the perivesical fat on T2 TSE with associated corresponding abnormal DWI/ADC signal and early enhancement on DCE through the whole muscularis propria, VI-RADS category is 5, and the muscle invasion is likely [5, 22].

When there is an extension of the tumor to the perivesical fat with the intermediate tumor signal disrupting the muscularis propria and seen beyond the confines of bladder wall on T2-weighted TSE images, the tumor is T3 (Fig. 5.5) [5, 14, 22]. High DWI signal with corresponding low ADC signal and increased enhancement of the tumor on the arterial phase extending into the perivesical fat beyond the confines of the bladder wall are also seen with T3 tumors [5, 14, 22]. Minimal to mild extension into the perivesical fat could still be present histopathologically, when the tumor involves the whole bladder wall without definite spread into the perivesical fat on MRI [5, 14, 22].

Fig. 5.5
figure 5

Bladder cancer. Transverse T2-weighted high resolution turbo spin echo image (a), transverse high resolution, small field of view diffusion weighted image (b) and its corresponding ADC map (c), transverse standard resolution, large field of view diffusion weighted image (d) and its corresponding ADC map (e), and transverse T1-weighted fat-suppressed postgadolinium excretory phase three-dimensional gradient echo (f) image show enhancing bladder mass with irregular contours and associated diffusion restriction along the right bladder wall (thick arrows, a–f). The mass extends all the way through the bladder wall to the perivesicle fat, which is suggestive of T3 tumor. Please note the presence of bilateral pelvic sidewall prominent lymph nodes (thin arrows, a–f). This tumor is classified as VI-RADS 5 tumor

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Invasion of the adjacent organs including the prostate, uterus, vagina and pelvic sidewalls, and abdominal wall represents T4 tumor (Fig. 5.6). T2 TSE is the dominant sequence for the evaluation of invasion of adjacent organs , and DWI and DCE are the adjunct sequences [14].

Fig. 5.6
figure 6

Bladder cancer. Transverse (a, b) and coronal (c) T2-weighted high resolution turbo spin echo images, transverse diffusion weighted image (d) and its corresponding ADC map (e), and transverse T1-weighted fat-suppressed postgadolinium interstitial phase three-dimensional gradient echo (f) image demonstrate a large irregular enhancing bladder mass with associated diffusion restriction involving the bladder dome, bilateral lateral walls, and trigone. The mass involves the right (arrow, a) and the left (arrow, b) ureterovesicle junctions with associated hydroureters (arrows, a, b). The mass involves the peritoneum (arrow, c) between the bladder dome and sigmoid colon, and this is suggestive of T4 tumor. There are also multiple centrally necrotic enlarged lymph nodes along the right-sided iliac chains (arrow, f). This tumor is classified as VI-RADS 5 tumor

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The detection of small tumors including the small flat or sessile lesions which are usually Tis, or tumors less than 1 cm is limited by MRI [14].

Variable signal intensity changes can be seen on T2-weighted TSE images including high-, intermediate-, and low-signal changes representing edema, inflammation, and fibrosis following post-biopsy and posttreatment changes [5, 14, 22]. Since these changes usually do not demonstrate diffusion restriction but show either high to intermediate signal on DWI and ADC map or low to intermediate signal on DWI and ADC map, DWI can be helpful for the differentiation of post-biopsy and posttreatment changes from the tumor [5, 14, 22].

N Staging

Internal iliac , external iliac, obturator, and presacral lymph nodes can be involved with N1-N2 lymph node-positive bladder cancer [15]. The common iliac chain lymph nodes are involved in N3 lymph node-positive bladder cancer [15]. More extensive retroperitoneal lymph node involvement above the level of common iliac chains is regarded as distant metastatic disease and staged as M1 [15].

The sensitivity and specificity of MRI including DWI in the identification of involved lymph nodes are 56–79% and 79–94% demonstrating limited accuracy of MRI [14, 29]. The presence of micrometastatic disease in lymph nodes equal to or smaller than 8–10 mm with normal morphology and lack of obvious diffusion restriction is a significant limitation leading to false-negative results [29,30,31,32]. Reactive and inflammatory changes of the lymph nodes mimicking metastatic lymph nodes are the other significant limitation leading to false-positive results due to overlapping MRI features including but not limited to size increase, increased enhancement, or obvious diffusion restriction [29,30,31,32].

However, diffusely increased heterogeneous T2 signal, focally increased homogeneous or heterogeneous T2 signal, focal or diffuse diffusion restriction, increased enhancement including focal or diffuse heterogeneous enhancement, asymmetrical increased cortical thickness, and asymmetrical shape compared to remaining lymph nodes or remaining part of the background normal lymph node architecture could be a clue for the diagnosis of lymph node involvement although none of these findings are specific.

Ultrasmall particle superparamagnetic iron oxide (USPIO) has the potential to identify metastatic involved lymph nodes) measuring less than 8–10 mm, which were otherwise could not be identified based on conventional size criteria [29, 32, 33]. These agents were taken by macrophages in normal lymph nodes, and lymph nodes showing benign inflammatory changes [29, 32, 33] demonstrating decreased T2 signal and appearing hypointense on T2 or T2*-weighted sequences [29, 32, 33]. However, metastatic lymph nodes are expected to show increased T2 signal and appear hyperintense on T2 or T2*-weighted sequences due to the lack of uptake by macrophages [29, 32, 33]. The sensitivity and specificity of USPIO for nodal staging in bladder cancer have been reported to be variable: 55–96% and 71–95% [14, 29, 32, 33], which could be due to false-negative results secondary to micrometastases in lymph nodes or false-positive results secondary to reactive hyperplasia, nodal lipomatosis, and insufficient uptake of USPIO.

Radiomics and Bladder Cancer

Radiomics is a developing translational field of imaging trying to find associations between extracted quantitative information obtained from imaging studies and clinical, laboratory, or histopathologic data with or without associated gene expression [6, 34, 35]. Quantitative information is extracted and analyzed by dedicated software, and this process is affected by image acquisition, postprocessing, and segmentation [6, 34, 35].

Quantitative features include shape features, first-order statistics, second-order statistics, and high-order statistics [6, 34, 35]. Shape features include dimensions, volume measurements or compactness, or surface features of tumors. First-order statistics use histogram-based features analyzing the intensities of voxels, their skewness (asymmetry), kurtosis (flatness), uniformity, and randomness (entropy) regardless of their spatial associations. Second-order statistics use textural features based on the interrelationships between adjacent voxels providing information on the spatial association of voxel intensities and lesion heterogeneity. High-order statistics use statistical methods to recognize any specific patterns, to suppress noise or to highlight details. Evaluation of these features can be enhanced by machine-learning techniques.

The role of radiomics analysis and features in the diagnosis and assessment of tumor response has not been still determined due to lack of sufficient data in the literature and limitations of this technique [34, 35]. The specific roles of individual parameters have also not been determined yet [34, 35]. A significant limitation for the use of radiomics features is the inability to have reproducible robust results without variability due to the dependence on acquisition technique and parameters [34]. Since the acquisition technique and parameters are very heterogeneous in the routine clinical practice, the radiomics analysis and its results are overall significantly and adversely affected [34]. Even the same studies done in the same scanner with the same parameters may end up giving different results depending on patient factors, contrast injection or enhancement changes, or scanning factors such as magnetic field inhomogeneities on MRI or imaging artifacts [34, 35]. Additionally, the lack of fully automated postprocessing and segmentation techniques with high accuracy also leads to variable results with low reproducibility [34]. Therefore, it is essential to describe the most useful radiomics parameters, define their roles in the diagnosis of tumors and assessment of treatment response, and determine the optimal ways to have reproducible robust results with the use of standard acquisition techniques and highly accurate fully automated postprocessing and segmentation techniques.

A limited number of studies on radiomics of bladder cancer have been reported in the literature. These initial studies used radiomics features for the staging of bladder cancer and assessing treatment response. Some specific studies demonstrated that radiomics features may play a role and may have high accuracy in the determination of tumor recurrence following TURBT [36], pathologic grade of tumor based on MRI [37], the muscle-invasive status of the tumor or extension of tumor to perivesical fat [38], and tumor volume changes following treatment [39, 40]. Due to limited number of studies, more research studies are needed to determine the role of radiomics in the assessment of bladder cancer.

Conclusion and Future Directions

Although imaging is essential for the diagnosis and staging of bladder cancer and assessment of tumor response, it is still limited, and therefore, direct visualization with cystoscopy and histopathologic assessment are the preferred standard methods for initial diagnosis and assessment of bladder wall involvement. High-spatial-resolution MR imaging of bladder cancer could be a promising technique for bladder cancer staging although its specific role has not been determined yet and this technique still needs validation. However, MR imaging techniques not only using high spatial resolution but also using higher contrast resolution in combination with motion resistant techniques may have higher potential to diagnose and stage bladder cancer and assess treatment response. Dual-source CT techniques by using different photon energies should also be studied for the assessment of bladder cancer. Radiomics features may also increase the accuracy of bladder cancer assessment and could be a helpful feature in radiologic assessments. Hybrid imaging techniques employing PET and pharmaceuticals are also promising and will be discussed in Chap. 7.