Healthy prostate epithelial cells have the specialized function of synthesizing and secreting large amounts of citrate that are dramatically reduced or lost in prostate cancer [96–99]. The loss of citrate in prostate cancer is intimately linked with changes in zinc levels that are extraordinarily high in healthy prostate epithelial cells [98, 100]. In healthy prostatic epithelial cells, the presence of high levels of zinc inhibits the enzyme aconitase, thereby preventing the oxidation of citrate in the Krebs’ cycle [98, 100]. Costello and Franklin have shown that these elevated levels of zinc are primarily due to increased expression of ZIP-type plasma membrane Zn uptake transporters (primarily Human ZIP-1) [99]. Human ZIP-1 is reduced and zinc levels are dramatically reduced in prostate cancer and the malignant epithelial cells, and there exists evidence that the loss of the capability to retain high levels of zinc is an important factor in the development and progression of prostate cancer [98, 100]. It is also believed that the transformation of prostate epithelial cells to citrate-oxidizing cells, which increases energy production capability, is essential to the process of malignancy and metastasis [97]. Additionally, both in vivo ¹H MRSI studies [90, 101–104] and ex vivo HR-MAS spectroscopic studies of biopsy samples and surgically removed prostate tissues [105, 106] have shown that the degree of decrease in citrate correlates with Gleason grade.

The elevation of choline-containing metabolites phosphocholine (PC), glycerophosphocholine (GPC), and free choline (Cho)] and the over- and under-expression of key enzymes in the Kennedy cycle have been associated with the progression and therapeutic response of a variety of human cancers including prostate [90]. Specifically, HR-MAS spectroscopic studies of ex vivo surgical and biopsy prostate tissues demonstrated elevated levels of ethanolamine and choline containing compounds and that elevated PC and GPC were the most robust predictors of prostate cancer presence [107], and both in vivo ¹H MRSI studies [90, 101–104] and ex vivo HR-MAS spectroscopic studies [105, 106] have shown that the degree of elevation of choline containing metabolites (PC and GPC) correlates with Gleason grade.

Healthy prostate epithelial cells also contain very high concentrations of polyamines, particularly spermine [90, 108, 109]. Polyamines are dramatically reduced in prostate cancer due to changes in the levels of expression of genes that regulate polyamine metabolism [90, 108]. The fact that choline and citrate change in opposite directions has led to the (choline  +  creatine)/citrate ratio (CC/C) being one of the most widely used metabolic biomarkers for detecting prostate cancer (54), and has been used in the majority of the current  ≈  320 publications on prostate MRI/MRSI [110]. It has also been demonstrated that when the CC/C ratio was  ≥  3 standard deviations above the normal value, there was minimal overlap between spectroscopic voxels from regions of cancer and healthy peripheral zone tissues [95], and the magnitude of elevation of the CC/C ratio has shown a correlation with cancer grade [90, 101, 111].

To date, studies investigating ¹H MRSI changes after therapy have focused on systemic therapy or the treatment of the entire prostate, rather than the ablation of dominant cancer foci within the prostate. These studies have indicated that the spectroscopic criteria used to identify residual/recurrent prostate cancer need to be adjusted due to a time-dependent loss of prostate metabolites following therapy. Specifically, time-dependent metabolic changes after androgen deprivation therapy (ADT), a common systemic therapy, have been studied using ¹H MRSI [112–114]. ADT is the cornerstone of the systemic management of prostate cancer [115], and patients who succumb to prostate cancer typically do so only after ADT has ceased to be effective. ADT can take several forms—including medical castration with LHRH agonists, first-generation anti-androgens, 5-alpha-reductase inhibitors, or various combinations of these therapeutics—and can last for years. It affects both healthy and malignant prostate cells, inducing apoptosis and resulting in increasing amounts of tissue atrophy with duration of therapy [116]. Prostatic citrate production and secretion have been shown to be regulated by androgens [96], and an early dramatic reduction of citrate and polyamines after initiation of complete hormonal blockade has been observed by ¹H MRSI [112–114]. There was slower loss of choline and creatine with increasing duration of hormone deprivation therapy [112]. This loss of prostatic metabolites correlates with the presence of tissue atrophy and has been considered a noninvasive indicator of effective therapy [113]. Time-dependent metabolic changes after ADT are of particular importance for selecting patients for focal therapy since many of these patients will be taking 5-alpha-reductase inhibitors, a form of ADT, which can result in significant changes in metabolism. In a recent serial multiparametric (T₂-MRI, DWI, ¹H MRSI) MR study of prostate cancer patients (N  =  9) on active surveillance taking dutasteride (3.5 mg once-daily), ¹H MRSI interpretation was confounded by the observation that citrate and polyamines decreased in healthy tissues while on dutasteride [117]. Thus, there was a bias to label healthy regions as likely cancer after dutasteride use. As the most dramatic changes in citrate and polyamines occurred in the first month, the one-month ¹H MRSI measures provided an improved estimate of cancer presence and volume, particularly for small cancers mixed with healthy tissue, which was the case for this early stage patient cohort. Similar time-dependent reductions in prostate metabolites have also been observed after external bean radiation and brachytherapy of the entire prostate [118, 119].

Studies have also demonstrated the ability of MRI/¹H MRSI to discriminate residual or recurrent prostate cancer from residual benign tissue and atrophic/necrotic tissue after cryosurgery [120–122], hormone deprivation therapy [112, 114], and radiation therapy [118, 123]. These studies have relied on elevated choline to creatine as a metabolic marker for prostate cancer since polyamines and citrate tend to disappear early after therapy in both residual healthy and malignant tissues (Fig. 14.3). Figure 14.3 shows a patient 9 years after external beam radiation therapy of the entire prostate. Consistent with effective radiation therapy, there were a number of spectroscopic voxels that demonstrated a complete loss of all prostate metabolites (metabolic atrophy). However, residual metabolic abnormalities (choline to creatine  ≥  1.5) persisted in the left midgland and this region was later confirmed as residual cancer by TRUS-guided biopsy. Two published MRI/¹H MRSI studies have demonstrated that three or more consecutive voxels having choline/creatine >1.5 resulted in the ability to predict the presence of cancer after radiation therapy with an accuracy of  ≈  80% [124, 125]. In the case of focal therapy, regions of untreated benign tissue, surrounding the treated cancerous lesions, should demonstrate high levels of citrate and polyamines. In this scenario, the choline  +creatine/citrate ratio would still be useful for the preservation of surrounding healthy prostate tissues surrounding the ablated region of cancer. The detection of residual cancer at an early stage following treatment and the ability to monitor the time course of therapeutic response would allow earlier intervention with additional salvage therapy [27, 126–131]. Alternatively, the lack of metabolic evidence of residual cancer after focal therapy could be used to demonstrate therapeutic success. This is a clinically important determination since residual benign tissue in the prostate will result in a nonzero serum PSA value, thereby diminishing its utility for predicting cancer presence relative to complete prostate therapeutic approaches such as radical prostatectomy.

¹H MRSI provides unique metabolic information about the evolution and progression of prostate cancer and its response to therapy, and as described below, the addition of this metabolic information to high spatial resolution anatomic information provided by MRI shows great promise in aiding in the selection, targeting, and monitoring of prostate cancer focal therapy. However, the results of the ACRIN trial 6659 of 1.5 T MRI/¹H MRSI of prostate cancer, as well as a number of publications, have demonstrated a clear clinical need to further improve the accuracy of the 1.5 T MRI/¹H MRSI examination, particularly when trying to risk stratify an early stage prostate cancer patient population prior to focal therapy. The ACRIN multi-institutional study showed that MRI alone and combined ¹H MRI/MRSI were of similar and modest accuracy (AUC of 0.60 for MRI and 0.58 for combined MRI/MRSI) in the localization of peripheral zone prostate cancer, and it did not confirm the primary hypothesis that the addition of ¹H MRSI to MRI would improve tumor localization. This hypothesis was based on a large number of prior single institution studies demonstrating that the addition of ¹H MRSI to MRI improves tumor localization [59, 132], tumor volume estimation [133], tumor staging for less experienced readers [87], and tissue characterization [90, 101, 111]. Given the preponderance of evidence that ¹H MRSI adds value to MRI in the evaluation of prostate cancer, it is reasonable to ask why the ACRIN trial study did not demonstrate such a benefit? There are several possible reasons. The ACRIN study population consisted of a contemporary series of North American patients undergoing radical prostatectomy, involving predominantly low-risk patients with small volume, low-grade disease. Many of the tumors pathologically detected in the ACRIN study were at or below the current spatial resolution of 1.5 T ¹H MRSI (≤ 0.5 cc) [101, 133]. Additionally, the application of ¹H MRSI to organs outside of the brain is technically very challenging, and the ACRIN study involved dissemination of endorectal ¹H MRSI to multiple sites and readers that had limited or no previous experience with it. That ACRIN successfully achieved this requirement for the study is a nontrivial accomplishment, and it is noteworthy that sites obtained studies of generally good spectral quality despite limited experience on a small number of test cases. Nevertheless, there were definite differences in the quality of ¹H MRSI data provided by the participating institutions. Additionally, the clinical translation of 1.5 T ¹H MRSI has been limited by insufficient spatial resolution to resolve small, low-grade cancers, relatively long acquisition times (17 min), and by technical issues. At 3 T, spatial resolution of ¹H MRSI can be increased  ≈  2-fold (0.16 cc, ≈ 5 mm on a side) and the spectral data acquired in 8 min with better spectral signal to noise as compared to 0.34 cc ¹H MRSI spectra acquired at 1.5 T in 17 min (Fig. 14.1c, d, e) [71]. Robust acquisition of ¹H MRSI has required the development of very specialized data acquisition techniques and protocols [134]. Through the use of an inflatable endorectal coil with a compound that matches the susceptibility of tissue and a pulse sequence (MLEV-PRESS) specifically designed for prostate spectroscopy at 3 T [71], high spatial and temporal resolution 3D MRI/¹H MRSI data can be obtained. Due to the pathologic and biologic complexity of prostate cancer, the addition of other high spatial resolution functional information to the MR staging examination will be key to patient selection and targeting focal therapy.

High spatial resolution DWI images can be easily and robustly acquired within a matter of minutes and therefore easily added to an MR staging examination, and the production of ADC maps quickly and easily performed [155]. The ease of acquisition and analysis combined with initial findings demonstrating clinical utility has led to great excitement over DWI’s role in prostate cancer focal therapy. However, in spite of significant differences between malignant and benign tissues in the peripheral zone before and after therapy, there is variability between patients as well as overlap of ADC values between malignant and benign prostatic tissues. This is not suprising since benign pathhologies such as prostatis and predominately stromal benign prostatic hyperplasia are often associated with pathologic changes that would lead to decreases in the extracellular space and corresponding reduction in ADC. The quantitative nature of DWI is also appealing; however, there remains a need for the test–retest validation of the quantitation of ADC values. There is also initial data suggesting that while ADC is increased in regions of prostate cancer after therapy, it remains lower than surrounding regions of treated benign and atrophic tissues [152, 153], but more studies after therapy are necessary to establish DWI utility for identifying residual disease and predict clinical outcomes.

The superior sensitivity of DCE-MRI compared with T₂ MRI, together with its high specificity, is arguably sufficient for its use for localizing cancerous lesions within the prostate for focal treatment [167]. Additionally, there are data suggesting that DCE-MRI can provide information on cancer aggressivenes, although there remains conflicting views as to how well DCE MRI parameters correlate with histological grade [188]. Similar to ¹H MRSI, the acquistion and analysis of DCE-MRI data of the prostate are more challenging and takes longer than T₂-weighted MRI and DWI. There also remains a need to determine whether qualitative vs. quantitative DCE-MRI parameters present the most robust predictive value and for the test–retest validation of DCE-MRI results. There is also initial evidence that DCE-MRI may be used to detect residual cancer after therapy based on a more dramatic contrast uptake and washout compared to surrounding regions of atrophy and residual benign tissues, but this needs to be proven in a larger number of studies.

Quantitative T₂ MRI studies can be easily added to a multiparametric examination, extending the examination by a matter of minutes, and T₂ maps of the prostate generated. The quantitative nature of these studies could overcome some of the specificity limitations of T₂-weighted MRI. However, the loss of ductal morphology in common benign pathologies (e.g., inflammation, stromal BPH) that coexist with prostate cancer will also reduce the specificity of quantitative T₂ MRI. Comparatively, much less is known about the clinical value of quantitative T₂ MRI in the assessment of prostate cancer, and like the other MRI approaches discussed, there remains a need for the test–retest validation of quantitative T₂ values obtained from the prostate.

A more accurate prediction of organ-confined prostate cancer at the time of diagnosis would allow the determination of whether “active surveillance” or “focal therapy” is appropriate for a given patient. At 1.5 T MRI, it has been demonstrated that anatomical features on MRI such as bulging of the prostate, obliteration of the rectoprostatic angle, and asymmetry of the neurovascular bundle can predict extracapsular extension (ECE), with specificity (up to 95%) but with low sensitivity (38%) [192]. Two studies have suggested that the addition of ¹H MRSI to MRI data can improve prostate cancer staging. In one study, it was found that tumor volume per lobe, estimated by ¹H MRSI, was significantly (P  <  0.01) higher in patients with ECE than in patients without ECE. Moreover the addition of an ¹H MRSI estimate of tumor volume to high specificity MRI findings for ECE [192] improved the diagnostic accuracy and decreased the interobserver variability of MRI in the diagnosis of ECE of prostate cancer [87].

An important advance in the staging of prostate cancer has been the development of multivariable risk prediction instruments such as the Partin tables [193] the CAPRA score [194] and various nomograms, which combine clinical stage, serum PSA levels, and grade of biopsies results to predict at the time of diagnosis the pathologic stage of the cancer and insignificant disease, respectively [195, 196]. Two recent studies demonstrated that addition of MRI/¹H MRSI findings could significantly improve the predictive ability of biopsy-based staging nomograms for predicting seminal vesicle invasion and organ-confined cancer. It was found that the nomogram plus endorectal MR imaging (0.87) had a significantly larger (P  <  0.05) area under the curve than either endorectal MR imaging alone (0.76) or the nomogram alone (0.80) [47]. In another study of prostate cancer patients prior to radical prostatectomy, 1.5 T MRI/¹H MRSI data were added to a nomogram for predicting (no ECE or SVI) in order to assess its incremental value. The contribution of MR/¹H MRSI findings to predicting organ-confined prostate cancer was also significant [50].

Due to increased screening using serum prostate-specific antigen (PSA) and extended-template transrectal ultrasound (TRUS)-guided biopsies, thousands of patients with prostate cancer are being identified at an earlier and potentially more treatable stage [197]. However, the risk of overdetection, detecting a cancer that would not become clinically significant during that patient’s lifetime if left untreated, has been estimated to vary between 15% and 84% [198–200]. Therefore there is an increased interest in “active surveillance,” but clinical parameters alone are not sufficient to predict a benign disease course. The addition of MRI/¹H MRSI data to clinical parameters has been shown to improve this prediction. In a study of 220 patients prior to surgery, the addition of MRI (AUC—0.803) and MRI/MRSI (AUC 0.854) to biopsy-based nomograms was found to significantly improve the prediction of indolent prostate cancer using a surgical definition of indolent disease (no ECE or SVI and <0.5 cm³ of cancer with no pattern 4 or 5 cancer) as the standard of reference [43]. In another study of 114 active surveillance patients who received a MRI/¹H MRSI at baseline, with a median follow-up time of 59 months, it was demonstrated that patients with a lesion suspicious for cancer noted on a MRI/¹H MRSI staging examination had a greater risk of Gleason upgrade at subsequent biopsy (HR 4.0; 95%CI 1.1–14.9) than patients without such a lesion [201] (Fig. 14.5). This study suggests that an abnormal MRI/¹H MRSI prostate examination at diagnosis that is suspicious for cancer may confer an increased risk of Gleason upgrade at subsequent biopsy, and may help counseling potential candidates about active surveillance, and whether they are more appropriate candidates for focal therapy. Specifically, MR imaging could play a role in selecting the subset of patients with indolent or subclinical disease that would be more appropriately managed with active surveillance vs. patients with more aggressive localized disease that would benefit from focal therapy. Clearly the higher spatial resolution functional MR data provided by DWI and DCE MRI could further improve this assessment. More recently, the D’Amico risk stratification was found to correlate with the degree of suspicion of prostate cancer on multiparametric MRI [202].

The reliable detection and localization of often small regions of clinically significant prostate cancer are therefore of critical therapeutic importance to focal ablative therapy since the patient population it will impact the most will be an early stage population [204]. T₂-weighted MRI alone has demonstrated good sensitivity but poor specificity in detecting cancer in the prostate [62, 78, 205]. Recent estimates using T₂-weighted sequences and endorectal coils vary from 60% to 96% [60]. The poor specificity is due to other benign pathologies (inflammation, stromal BPH) and therapy also causing a loss of ductal morphology and low T₂ on MRI [206]. Additionally, infiltrating prostate cancer may not cause a reduction in normal glandular morphology and therefore will not be hypointense on MRI [206]. Similar to imaging at 1.5 T, T₂-weighted image quality, prostate cancer localization and staging are significantly improved at 3 T with the use of an endorectal coil compared with a external phased array coil [207]. Identifying prostate cancer within the central gland is particularly difficult for MRI due to the overlap of T₂-weighted signal intensity in predominately stromal BPH. In a recent study of 148 prostate cancer patients prior to radical prostatectomy, MR imaging alone detected zone prostate cancers with modest accuracy with areas under the reader operator curve (AUC) ranging from 0.73 to 0.75 [208].

The higher specificity of ¹H MRSI to metabolically identify cancer can be used to improve the ability of MRI to identify the location and volume of cancer within the prostate [132, 133, 209–212]. A study of 53 biopsy-proven prostate cancer patients prior to radical prostatectomy and step-section pathologic examination demonstrated a significant improvement in cancer localization to a prostatic sextant (left and right—base, midgland, and apex) using combined MRI/¹H MRSI vs. MRI alone [132]. A combined positive result from both MRI and MRSI indicated the presence of tumor with high specificity (91%), while high sensitivity (95%) was attained when either test alone indicated the presence of cancer [132]. The addition of positive sextant biopsy findings to concordant MRI/MRSI findings further increased the specificity (98%) of cancer localization [212]. However, more recent studies in early stage prostate cancer patients have indicated that combined 1.5 MRI/MRSI does poorly at detecting and localizing small low-grade tumors [101, 133, 209]. One study demonstrated that overall sensitivity of MR spectroscopic imaging was 56% for tumor detection, increasing from 44% in lesions with Gleason score of 3+3 to 89% in lesions with Gleason score greater than or equal to 4+4 [101]. The inability to detect small low-grade tumors by 1.5 T ¹H MRSI is primarily due to the partial volume averaging of surrounding benign tissue in spectroscopic volumes containing cancer due to the relatively coarse spatial resolution of 1.5 T MRSI (0.34 cc, ≈ 7 mm on a side).

In a recent meta-analysis of the 1.5 T MRI/¹H MRSI literature, 31 studies (1,765 patients) were identified in the literature; 16 studies (17 populations) with a total of 581 patients were suitable for meta-analysis [110]. Nine combined MRI/¹H MRSI studies (10 populations) examining men with pathologically confirmed prostate cancer (297 patients; 1,518 specimens) had a pooled sensitivity and specificity on prostate subpart level of 68% (95% CI, 56–78%) and 85% (95% CI, 78–90%), respectively. Compared with patients at high risk for clinically relevant cancer (six studies), sensitivity was lower in low-risk patients (four studies) (58% [46–69%] vs. 74% [58–85%]; P  >  0.05) but higher for specificity (91% [86–94%] vs. 78% [70–84%]; P  <  0.01). Seven studies examining patients with suspected prostate cancer at combined MRI/MRSI (284 patients) had an overall pooled sensitivity and specificity of 82% (59–94%) and 88% (80–95%). In the low-risk group (five studies), these values were 75% (39–93%) and 91% (77–97%), respectively.

DWI and DCE images can be acquired within a matter of minutes at very high spatial resolution (0.9  ×  1.8  ×  4 mm³), allowing their addition to a clinically reasonable MRI/¹H MRSI examination and potentially improving MR detection of small low-grade tumors [155]. DCE imaging at 1.5 T and 3.0 T demonstrated similar sensitivities (73% and 73%, respectively) and specificities (81% and 77%, respectively) for identifying cancer within the prostate [62, 213]. In another study of prostate cancer patients who received an MRI/¹H MRSI/DCE examination prior to radical prostatectomy, it was demonstrated that reader accuracy in tumor detection was significantly (P  <  .01) better for 3D MRSI (AUC  =  0.80) and DCE (AUC  =  0.91) than T₂-weighted imaging (AUC 0.68) [59]. However, no attempt was made to determine the accuracy when all 3 techniques were combined. In a recent study, a combination of T₂-weighted imaging, DWI, DCE, and MRSI was used to identify the regions suspicious for prostate cancer that were biopsied under MR guidance. They showed that all areas that were determined to be suspicious or indeterminate on T₂-weighted MRI were suspicious on at least one advanced imaging technique and that the combination of the 3 advanced techniques depicted more prostate cancer areas than the combination of any 2 of them [214]. 3 T DWI studies also demonstrated good sensitivity (84%) and specificity (80%) for identifying cancer within the prostate [56], and the overall accuracy (AUC  =  0.89) was found to be better than that of T₂ imaging (AUC  =  0.82) [51]. A positive correlation was also found between ¹H MRSI and DWI findings for prostate cancer [215]. Another study that utilized combined DWI and MRSI of 61 prostate cancer patients demonstrated that the combination (AUC  =  0.85) performed significantly better than MRSI alone (AUC  =  0.74; P  =  .005) and was also better than alone (AUC  =  0.81, P  =  .09) for differentiating between benign and malignant ROIs in the PZ [216].

The reliable assessment of the extent or volume of prostate cancer is also critical for MR-guided focal ablative therapy, and the ability to accomplish is challenging due to the relatively early stage population that will most likely be treated. Two recent studies suggest that MRI/¹H MRSI and DCE imaging may noninvasively provide estimates of cancer volume at diagnosis. One study demonstrated that for nodules greater than 0.5 cm³, tumor volume measurements by MRI, ¹H MRSI, and combined MRI and MRSI were all positively correlated with histopathologic volume (Pearson’s correlation coefficients of 0.49, 0.59, and 0.55, respectively), but only measurements by ¹H MRSI and combined MRI/¹H MRSI reached statistical significance (P  <  0.05) [133]. The addition of ¹H MRSI to MRI also increased the overall accuracy of prostate cancer tumor volume measurement, although measurement variability still limited consistent quantitative tumor volume estimation, particularly for small tumors (<0.5 cm³) [133]. Another study demonstrated that DCE imaging determined the volume of smaller foci of prostate cancer with greater overall accuracy than MRI/¹H MRSI. Sensitivity, specificity, and positive and negative predictive values for cancer detection by DCE imaging were 77%, 91%, 86%, and 85% for foci >0.2 cc, and 90%, 88%, 77%, and 95% for foci greater than 0.5 cc, respectively [57]. In another study, the sensitivity and specificity of detecting intraprostatic prostate cancer by DCE MRI was determined to be 86% and 94%, respectively, with a ROC of 0.874 [178]. Mean volume of DCE-MRI detected and missed cancers were 2.44 mL (0.02–14.5) and 0.16 mL (0.005–2.4), respectively [178]. In a study of 42 patients, the addition of DWI to T₂ MRI significantly improved the accuracy of prostate peripheral zone tumor volume measurement [217]. Specifically, using a ADC cutoff of 0.0016 mm²/s for cancer, the concordance correlation coefficient of combined T₂-MRI and DWI MR imaging was significantly higher (P  =  .006) than that of T₂-MRI alone.

Numerous studies reported in the literature have used the results from multiparametric MR staging examinations, performed prior to the TRUS biopsy, to identify regions of MRI suspicious cancer for subsequent real-time TRUS-guided biopsy [3, 226–229]. This MRI targeted biopsy approach has been utilized in several studies of patients with prior negative biopsies, and rising PSA. These patients typically have cancers in locations such as the anterior aspect of the prostate that are difficult to biopsy or in patients with large prostates where the sampling error of TRUS-guided systematic biopsy approaches are reduced. Specifically, in two studies, the accuracy of cancer detection of MRI/¹H MRSI targeted biopsy in men with a prior negative biopsy was reported to be  ≈  80% [226, 227]. Combining DCE-MRI with ¹H MRSI demonstrated a further improvement to guide biopsy needles to cancer foci in patients with previously negative TRUS biopsy [230, 231]. The combination of ¹H MRSI and DCE-MRI yielded 93.7% sensitivity, 90.7% specificity, 88.2% PPV, 95.1% NPV, and 90.9% accuracy in detecting prostate carcinoma in a prior negative biopsy population [231]. In addition to improving cancer detection, MRI targeted, TRUS-guided biopsies also improved estimates of cancer volume and pathologic grade compared to a TRUS-guided systematic biopsy approach [232]. Additionally, combined T₂-weighted and DCE-MRI was shown to be useful for guiding TRUS biopsies toward areas containing recurrent cancer after HIFU [233] and radiation therapy [164]. It is clear that the MR-directed TRUS biopsy approach is limited by inaccuracy in targeting small tumors as there is guesswork involved in triangulating lesions seen on multiparametric MRI to ultrasound. To date studies have added MR targeted biopsies to a systematic TRUS biopsy protocol, and whether a targeted approach alone is clinically sufficient requires further study [229]. The guesswork involved with transferring the multiparametric MR identified foci of cancer onto ultrasound data can be overcome by performing MRI-guided biopsy within the bore of the magnet.

The recent development and implementation of MR-guided biopsy devices allow for a direct means of taking a biopsy of prostate cancer identified using multiparametric data. As shown in Fig. 14.6, the current commercially available MR-guided biopsy device (DynaTRIM, Invivo Corporation, Orlando, FL) uses a transrectal biopsy approach. The patient is placed in the prone position inside the magnet. A body phased array coil is placed on the patient’s lower back and abdomen, and a MR visible needle guide that is attached to the MR biopsy device is inserted into the rectum (Fig. 14.6). Based on imaging findings, the MR-compatible biopsy device is adjusted using software that interfaces with the scanner and manual adjusts in all three spatial dimensions to obtain a biopsy core from the region of interest within the prostate. The needle guide is tracked by fast anatomic MR imaging during the adjustment of the biopsy device. Several studies have demonstrated the clinical potential of MRI-guided biopsies for detecting clinically significant prostate cancer prior to therapy [234–239] and residual disease after therapy [182]. Prior to therapy, the detection rate of multiparametric 3 T magnetic resonance imaging-guided biopsy was 59% (40 of 68 cases), which was significantly greater than transrectal ultrasound (15%) and 37 of the 40 patients (93%) with positive biopsies were considered highly likely to harbor clinically significant disease [238]. In a study of 24 patients with rising PSA after external beam radiation therapy, multiparametric MR identified areas of residual/recurrent prostate cancer with a positive predictive value of 75% based on MR targeted biopsies of the MR suspicious area [182].