Kyle K. Yu

IMAGING PROSTATE CANCER

The clinical management of prostate cancer continues to be one of the most controversial areas in medicine, with no consensus on the need for cancer screening, choice of diagnostic tests for pretreatment evaluation, and the need for and appropriateness of treatment for any stage of disease. 66 Controversies in management can be attributed to several unique biologic features of the disease. 77 For example, many prostate cancers do not lead to serious morbidity or death. Autopsy studies have shown that 30% to 46% of men older than age 50 have microscopic prostate cancer, yet less than 20% of men develop clinical prostate cancer in their lifetime. 36,66 Unlike other cancers (e.g., lung, colon, breast, or ovarian cancer), which behave aggressively and are more rapidly and uniformly fatal if untreated, prostate cancer behaves in a less predictable manner. Some cancers are small, well differentiated, and unlikely to cause clinically significant disease, whereas others are large, poorly differentiated, and likely to metastasize, causing death. Despite recent advances in the diagnosis, pretreatment evaluation, and treatment of prostate cancer, significant gaps in knowledge of the underlying pathophysiology of this disease remain. Several major obstacles impede the optimal clinical management of prostate cancer. The first obstacle, related to early detection, is the inability of screening tests to differentiate subclinical disease from clinically significant prostate cancer. Although there is evidence suggesting that most (85% to 90%) cancers detected through prostate cancer screening programs represent clinically significant rather than insignificant disease and are detected at an earlier stage of disease, the feasibility of prostate cancer screening in the general population remains controversial, and the costs of undertaking screening in all men over age 50 years far exceeds presently available health care funds. 40,54,77,85 The second obstacle is related to treatment planning. There are limitations of currently available tumor prognostic factors in differentiating indolent from aggressive disease. Although a number of tumor prognostic factors (e.g., tumor volume, grade, and stage) can generally predict disease at either end of the spectrum, most cancers fall into an intermediate range, where it is difficult to distinguish those cancers likely to progress from those that can be observed. 55,79 There continues to be intense debate about the ability of currently available tumor prognostic factors accurately to assign patients to appropriate risk and treatment categories. 77 Prostate cancer is usually suspected due to an abnormal digital rectal examination (DRE) or elevated serum prostate-specific antigen (PSA) level (Fig. 1). American Cancer Society recommendations for the annual cancer prevention check-up includes DRE and serum PSA testing for men older than 50 years or for younger men at increased risk (black race or family history of prostate cancer) for the disease. 47 Imaging provides additional information in patients with a histologic diagnosis of prostate cancer, but imaging findings alone are not sufficient for the primary diagnosis of prostate cancer. The diagnosis of prostate cancer depends on the histopathologic evaluation of tissue specimens obtained from digitally or transrectal ultrasound (TRUS)–guided prostate biopsies (see Fig. 1). 39 Systematic (sextant) core biopsies of the prostate are recommended to maximize the diagnostic yield of biopsy and to allow estimation of tumor grade and volume. 60

The prostate: MR imaging and spectroscopy. Present and future.

The applications of combined MR imaging and MR spectroscopic imaging of prostate cancer have expanded significantly over the past 10 years and have reached the point of clinical trial results to test robustness and clinical significance. MR spectroscopic imaging extends the diagnostic evaluation of prostate cancer beyond the morphologic information provided by MR imaging throughout the detection of cellular metabolites. The combined metabolic and anatomic information provided by MR imaging and MR spectroscopic imaging has allowed a more accurate assessment of the presence, location, extent, and aggressiveness of prostate cancer both before and after treatment. This information has already demonstrated the ability to improve therapeutic planning for individual prostate cancer patients and shows great promise in the assessment of therapeutic response and the evaluation of new treatment regimes.

Identification of myocardial reperfusion with echo planar magnetic resonance imaging. Discrimination between occlusive and reperfused infarctions.

BackgroundThe current treatment of many cases of acute myocardial infarction involves the use of thrombolytic agents. Evaluation of this therapy requires determination of the success of reperfusion and assessment of the presence and extent of infarction in the reperfused territory. The present study was designed to simulate in rat models several possible outcomes of reperfusion therapy: (1) successful reperfusion and absence of myocardial infarction, (2) successful reperfu-sion and presence of myocardial infarction, and (3) unsuccess-ful reperfusion. The usefulness of contrast-enhanced fast magnetic resonance (MR) imaging in defining the success of reperfusion was investigated. The dynamic effects were examined of low and high doses of gadolinium-BOPTA/dimeglu-mine (Gd-BOPTA/dimeg) on myocardial signal using MR inversion recovery echo planar imaging (IR-EPI) and gradient recalled echo planar imaging (GR-EPI), respectively. Methods and ResultsRats were subjected to one of the following regimens: reperfused reversible myocardial injury (n=9), reperfused irreversible myocardial injury (n=9), and occlusive infarction (n=9). MR echo planar images were acquired every 1 or 2 seconds before, during, and after administration of Gd-BOPTA/dimeg. In all groups, normal myocardial signal was sharply increased on IR-EPI and decreased on GR-EPI at the peak of the bolus, followed by a gradual decline to baseline. In animals subjected to reperfused reversible myocardial injury, normal and previously ischemic regions were indistinguishable during and after the passage of Gd-BOPTA/dimeg. On the other hand, enhancement of reperfused irreversibly injured myocardium was delayed but increased steadily to a higher level than normal myocardium on IR-EPI. The reperfused irreversibly injured myocardium was identified on IR-EPI as a zone of high signal (hot spot). On GR-EPI, signal loss in reperfused irreversibly injured myocardium was significantly less compared with normally perfused myocardium. In animals with occlusive infarctions, there was no change in signal intensity over the ischemic region on either IR-EPI or GR-EPI. Occlusive infarction was identified as zones of either low (cold spot) or high (hot spot) signal compared with normal myocardium, depending on MR pulse sequence and dose of the contrast medium. ConclusionsThe transit of Gd-BOPTA/dimeg monitored by fast MR imaging techniques can be used to distinguish between reperfused reversibly and reperfused irreversibly injured myocardium and between occlusive and reperfused infarctions.

THE PROSTATE: DIAGNOSTIC EVALUATION OF METASTATIC DISEASE

One of the single most important considerations in clinical management of the patient with prostate cancer is whether or not metastatic disease is present. The identification of metastatic disease in a patient with newly diagnosed prostate cancer represents an absolute contraindication to definitive local therapies such as radial prostatectomy or radiation therapy. Similarly, the identification of metastatic disease in a patient with disease recurrence after definitive local therapy represents an absolute contraindication to salvage radiotherapy or cryosurgery. Patients with metastatic disease do not benefit from definitive therapy, and the cost and morbidity associated with such treatment should therefore be avoided in these patients. Because of the significance of metastatic disease to clinical management, it is important for the diagnostic radiologist to be aware of important considerations in the metastatic work-up of patients with newly diagnosed prostate cancer and patients with suspected cancer recurrence after definitive local therapy.

Detection of extracapsular extension of prostate cancer: role of fat suppression endorectal MRI.

PURPOSE The purpose of this work was to compare the efficacy of fat-suppressed and non-fat-suppressed fast spin echo (FSE) endorectal MRI in the detection of extracapsular extension (ECE) of prostate cancer by experienced and inexperienced readers. METHOD Seventy-nine patients with biopsy-proven prostate cancer underwent axial FSE T2-weighted endorectal MRI of the prostate prior to radical prostatectomy. Twenty-one patients were imaged with frequency-selective fat suppression, and 58 were imaged without fat suppression. All images were retrospectively and independently reviewed by two readers of different experience levels who were blinded to clinical and pathological findings. Readers assessed the presence or absence of ECE on a 5 point scale for each side of the prostate, and step-section pathology was used as the standard of reference in all patients. Receiver operating characteristics analysis was used to compare the performance of fat-suppressed and non-fat-suppressed images by both readers. RESULTS ECE was present in 33 of 79 (42%) patients. The more experienced reader demonstrated better diagnostic performance (p < 0.05) than the less experienced reader in terms of sensitivity and area under the ROC curve (Az) for MRI without fat suppression. Use of frequency-selective fat suppression did not result in any significant improvement in diagnosis of ECE compared with MRI without fat suppression for either the experienced (Az 0.81 vs. 0.79) or the inexperienced (Az 0.76 vs. 0.68) reader. CONCLUSION Even when reader experience is considered, use of frequency-selective fat suppression did not significantly improve the diagnosis of ECE by MRI. The decision to use fat suppression and the selection of a fat suppression technique can be left to the discretion of the individual reader.

Comparison of T1-enhancing and Magnetic Susceptibility Magnetic Resonance Contrast Agents for Demarcation of the Jeopardy Area in Experimental Myocardial Infarction

RATIONALE AND OBJECTIVES.This study compared the areas demarcated by a T1-enhancing agent, Gd-DTPA-BMA, and a magnetic susceptibility agent, Dy-DTPA-BMA, with 201thallium autoradiography (indicator of perfusion) and postmortem histochemical staining with triphenyltetrazolium chloride (TTC)(indicator of infarction). METHODS.Thirteen rats were subjected to coronary artery occlusion for 3 to 4 hours before acquisition of four sets of electrocardiogram-gated spin-echo magnetic resonance (MR) images: T1-weighted images before and after 0.2 mmol/kg Gd-DTPA-BMA; and T2-weighted images before and after 0.3 mmol/kg Dy-DTPA-BMA. After MR imaging, intravenous 201thallium delineated the area of decreased myocardial perfusion. At autopsy, TTC staining delineated the area of myocardial infarction. RESULTS.A myocardial region in the distribution of the occluded artery was delineated as a hyperintense area (“hotspot”) by Dy-DTPA-BMA and as a hypointense area (“coldspot”) by Gd-DTPA-BMA. The hyperintense area demarcated by Dy-DTPA-BMA (51 ± 3% of the area of the midequitorial slice of the left ventricle) showed a closer relationship to the area of decreased myocardial perfusion (jeopardized area) (46 ± 3%), determined by 201thallium autoradiography, than the area of myocardial infarction (36 ± 4%), determined by histochemical staining. However, the hypointense area demarcated by Gd-DTPA-BMA (29 ± 2%) did not relate as closely to the area of decreased myocardial perfusion (slope = 0.54) or the area of myocardial infarction (r = 0.46). CONCLUSIONS.The abnormal myocardial area delineated by the magnetic susceptibility agent showed a closer relationship to the area of deficient myocardial perfusion (jeopardy area) after coronary occlusion than that defined by T1-enhancing contrast media.

Delineation of acute myocardial infarction with dysprosium DTPA-BMA: Influence of dose of magnetic susceptibility contrast medium☆☆☆

OBJECTIVES The contrast enhancement of acutely infarcted myocardium produced by the nonionic magnetic susceptibility-enhancing agent dysprosium diethylenetriamine pentaacetic acid-bis-methylamide (DyDTPA-BMA [S-043 Injection]) was assessed in the current study to establish the lowest dose that would yield optimal contrast between normal and acutely infarcted myocardium. BACKGROUND Magnetic susceptibility contrast agents enhance differences between normal and ischemic tissue by reducing the signal of the normally perfused tissue to which they distribute. METHODS Acute myocardial infarctions were produced by ligation of the left coronary artery. At 3 to 4 h after occlusion, a dose of 0.1, 0.3 or 0.5 mmol/kg of DyDTPA-BMA was injected intravenously into eight rats each in group 1, 2 or 3, respectively; a fourth group of seven rats served as a control group. Nuclear magnetic resonance (NMR) transverse relaxation time (T2)-weighted images (electrocardiographically gated to every 5th beat, echo delay time [TE] = 60 ms) were acquired before and for 1 h after administration of contrast agent. RESULTS Images obtained before the injection of contrast agent showed moderate differences in signal intensity between normal and infarcted myocardium (p < 0.05). The contrast enhancement and the duration of delineation between infarcted and normal myocardium produced by this agent were dose dependent. At doses of 0.1, 0.3 and 0.5 mmol/kg, DyDTPA-BMA produced signal loss in normal myocardium: 63 +/- 5%, 41 +/- 4% and 28 +/- 4% of the baseline values, respectively, without any significant reduction in signal intensity of the infarcted region. The reduction in signal of normal myocardium and delineation of the infarct persisted for 5 min at a dose of 0.1 mmol/kg, for 20 min at a dose of 0.3 mmol/kg and for 40 min at a dose of 0.5 mmol/kg. No change in signal intensity or signal intensity ratio between normal and infarcted myocardium was observed in the control group during the same observation period. CONCLUSIONS These results suggest that low doses of this agent, comparable to those of longitudinal relaxation time (T1)-enhancing agents, can delineate acutely infarcted myocardium. A dose of 0.3 mmol/kg of DyDTPA-BMA (S-043 Injection) provides reasonably persistent demarcation of acute myocardial infarction. Because this dose dramatically suppresses the NMR signal of normal myocardium, it shows the infarcted region as a region of high intensity (bright spot) on NMR images.

The use of contrast-enhanced magnetic resonance imaging to define ischemic injury after reperfusion. Comparison in normal and hypertrophied hearts.

Lauerma K, Saeed M, Wendland MF, Derugin N, Yu KK, Higgins CB. The use of contrast-enhanced magnetic resonance imaging to define ischemic injury after reperfusion: comparison in normal and hypertrophied hearts. Invest Radiol 1994; 29:527-535. RATIONALE AND OBJECTIVES.Magnetic resonance imaging (MRI) was used to demonstrate the infarction size in reperfused ischemic myocardium of normal and hypertrophied hearts, and to test the hypothesis that hypertrophied hearts manifest greater susceptibility to ischemia. METHODS.Normal rats (n=11) and rats subjected to left ventricular hypertrophy (LVH) by aortic banding (n=13) were studied. After 7 weeks, the left coronary artery was occluded for 25 minutes and reperfused for 1 hour before MRI. Electrocardiogram-gated spin-echo images were acquired before and after administration of 0.3 mmol/kg gadoteridol. To quantify the hyperintense area demarcated by gadoteridol, 3 transaxial images were acquired at different levels. Jeopardy and infarcted areas were measured in the same three slices postmortem using blue dye and triphenyltetrazolium chloride (TTC) stain, respectively. RESULTS.Before administration, there was no significant difference in signal intensity between nonischemic (0.42 ± 0.03 arbitrary units) and ischemic (0.41 ± 0.03) myocardium in either group. After gadoteridol injection, signal intensity of the reperfused injured region was higher than that of nonischemic myocardium (1.48 ± 0.16 vs. 0.72 ± 0.06, P < .05). Magnetic resonance delineation of the hyperintense area persisted for at least 30 minutes. The size of the hyperintense area was larger in LVH than in control hearts (25 ± 5% vs. 7 ± 3% of LV surface area, P < .05) and did relate closely to the area of myocardial infarction (r=.97), but not with the jeopardy area (r=.42). On TTC staining, the infarction size also was significantly greater in LVH than in normal group (18 ± 5% vs. 5 ± 2% of LV surface area, P < .05). The jeopardy areas of normal and LVH hearts showed no significant difference (46 ± 2% vs. 47 ± 3%). CONCLUSION.Magnetic resonance imaging confirms the concept that reperfused myocardial injury is larger in LVH than normal hearts after brief coronary occlusion. Contrast-enhanced MRI can define the size of reperfused myocardial injury. Thus, MRI is a suitable technique to assess conditions accentuating ischemic injury.

Shared patient analysis: a method to assess the clinical benefits of patient referrals.

Background.Referral to specialized physicians or institutions often is deemed necessary in clinical medicine, but no method exists to assess the clinical benefit of such referrals. Objectives.To describe a method, which is shared patient analysis, to measure the expected improvement in clinical management associated with referrals and to apply that method in the field of abdominal and pelvic oncological radiology. Subjects.All patients referred, during a 4-year period, to surgical oncologists at four academic centers (the referral providers, or RPs) with radiographs performed before referral at a community site (the initial providers, or IPs). Patients (n = 396) for whom both the IP interpretation and a final diagnosis was available were eligible. All IP and RP readings were placed in random order and presented to surgical oncologists, who then recommended a treatment course. Measurements.Diagnostic accuracy of the IP and RP readings and the proportion of patients who were assigned to an appropriate treatment by the oncologist were determined. Results.When the indication for imaging was primary diagnosis or staging, the kappa for presence of cancer was 0.70. When the indication was cancer follow-up, the kappa for presence of recurrent/progressing cancer was 0.66. There were disagreements between the IP and RP radiologists over the interpretation of 162 films, with the RP radiologists being correct in 153 (94%). Had the patients been treated using IP readings, there would have been 19 more inappropriate surgeries and 19 more admissions (both P <0.05) than if the oncologists had based their recommendations on RP readings. Conclusions.The technique of shared patient analysis permits assessment of the clinical benefits associated with referrals.

Verapamil reduces the size of reperfused ischemically injured myocardium in hypertrophied rat hearts as assessed by magnetic resonance imaging

Contrast-enhanced magnetic resonance (MR) imaging was used to detect and quantify the extent of myocardial injury after a brief coronary occlusion and reperfusion in response to verapamil treatment in a rat model of left ventricular hypertrophy (LVH). Two groups of rats were prepared by banding the abdominal aorta for 7 to 8 weeks to produce LVH. Group 1 (n = 13) received oral verapamil for 3 days, whereas group 2 (n = 13) received no therapy. Before MR examination was performed, each rat was subjected to 25 min of coronary artery occlusion followed by 1 hour of reperfusion. T1-weighted spin echo images were acquired before and after 0.3 mmol/kg gadoteridol was injected. Three images were acquired at contiguous levels of the LV and used to estimate the size of the myocardial injury. The size of the infarcted region was demarcated at postmortem examination by using triphenyltetrazolium chloride dye (TTC). Before contrast medium was administered, no significant difference in signal intensity was seen between nonischemic and reperfused ischemically injured myocardium. After gadoteridol was injected, a hyperintense zone indicative of myocardial injury was observed in 8 of 13 rats treated with verapamil and in all untreated animals. The size of the injury was significantly larger in untreated hearts than in hearts treated with verapamil as defined on MR images (25% +/- 5% vs 18% +/- 5%, p < 0.05) and TTC staining (12% +/- 4% and 4% +/- 1%, p < 0.05). Good correlation (r = 0.91) was found between the two measurements. No significant difference in the size of jeopardy area was seen between the two groups as (defined by blue dye infusion). In conclusion, contrast-enhanced MR imaging is a suitable technique to evaluate the effects of therapies applied to reduce myocardial injury. Verapamil can cause reduction in the extent of ischemic injury after reperfusion of hypertrophied myocardium.