Duplex Doppler ultrasonography (DDU) and dynamic infusion pharmacocavernosometry are the conventional diagnostic methods currently used to assess veno-occlusive hemodynamic status of patients with erectile dysfunction (ED). Dynamic infusion pharmacocavernosography is the standard method for demonstrating and visualization of venous leakage. To assess the potential application and utility of magnetic resonance imaging (MRI) in demonstrating and visualizing venoocclusive dysfunction in patients with ED. A total of 28 patients, (32-56 years of age; mean 43.4 [+ or -] 7.2 years), with clinical symptoms of veno-occlusive ED participated in this study. All patients have undergone DDU and dynamic infusion pharmacocavernosometry and pharmacocavernosography to assess presence of venous leakage. Patients were then evaluated with MRI and enhancement by intracavernous injection of paramagnetic contrast agent and erection was induced by intracavernosal injection of pharmacological agents. Diagnosis of ED patients with venous leakage was confirmed in all 28 patients using DDU and dynamic infusion cavernosometry-cavernosography (DICC). Venous leakage was documented by conventional DICC in 21 of 28 patients (75%). Venoocclusive dysfunction in all patients was also assessed by MRI to localize distal, proximal or mixed locations of draining veins from the corpora cavernosa. MRI visualized venous leakage patients, in which DICC did not confirm venous leakage. MRI may be a useful diagnostic tool for assessing venoocclusive dysfunction in ED patients and may improve diagnosis of venous leakage visualization.
doi:10.1038/sj.ijir.3901607; published online 6 September 2007
Keywords: diagnostic testing; veno-occlusive erectile dysfunction; venous leakage; dynamic infusion pharmacocavernosography; magnetic resonance imaging
Various pathologies disrupting penile hemodynamics, including arterial insufficiency, venoocclusive dysfunction or mixed arterial and veno-occlusive dysfunctions, are responsible for failure to initiate, to fill or to maintain erectile function. (1-4) Arterial insufficiency of the hypogastric-cavernous arterial bed is most commonly a manifestation of generalized peripheral vascular disease or cardiovascular disease but may also occur following blunt perineal or penile trauma. (5) The veno-occlusive mechanism depends on the integrity and function of the cavernosal smooth muscle and on the elastic properties and function of the tunica albuginea. (6) Corporal veno-occlusive dysfunction refers to a dysfunction in the normal veno-occlusive function. (5) The primary problem may be due to loss of elasticity of the tunica albuginea, fibrosis or degeneration of the intracavernous smooth musculature, increase of collagen fibers as well as lack of neurotransmitters. (7) Corporal veno-occlusive dysfunction is a pathophysiologic factor in 20-35% patients with ED.
Duplex Doppler ultrasonography (DDU) is a useful tool in the diagnosis and assessment of penile hemodynamic integrity in the penile arterial bed utilizing (8) cavernosal artery peak systolic velocity values. Corporal veno-occlusive integrity can be estimated during DDU by measuring end diastolic velocity and vascular resistance values; however, this method is associated with false negative and false positive diagnoses of vasculogenic ED. (9) In particular, false negative results of DDU are often reported in young patients. (10) The standard for assessment of hemodynamic integrity is dynamic infusion cavernosometry-cavernosography (DICC). (3) In particular, pharmacocavernosography is the only diagnostic procedure that enables the visualization of the venous leakage from the corpora cavernosa.
Diagnosis of several penile conditions has been reported using magnetic resonance imaging (MRI), these include the identification of anatomic structures of the penile shaft and crurae, and pathological tissue processes such as hematomas and damaged erectile tissues after blunt injury of the perineum. (11) MRI may visualize pathological changes in the tunica albuginea as well as evaluate the arterial supply of penis in patients with ED. (12-14) Stehling et al. (12) have utilized magnetic resonance angiography (MRA)/MRI to delineate internal pudendal and penile arteries. The goal of this study was to evaluate the potential use of MRI as a diagnostic tool for assessment of venous leakage in men with venous ED.
Materials and methods
A total of 28 men with ED and suspected veno-occlusive ED (ages 32-56 years, mean 43.4 [+ or -] 7.2 years) were selected from a total cohort of patients with ED. These patients agreed to participate in this study and were able to pay for the investigations. These patients had complaints of insufficient penile rigidity with rapid detumescence during or before intercourse. All men had sexual partners and failed initial management with selective type 5 phosphodiesterase (PDE-5) inhibitors treatment due to their co-morbidities or the severity of the main disease. Every patient with ED completed the self-administrated questionnaire, the International Index of Erectile Function (IIEF). This prospective study was approved by Hospital's Ethics Committee and all the patients signed an informed consent.
Patient's evaluation included sexual and medical histories, physical examination with psychological and neurologic examination, serum glucose, testosterone and prolactin levels. The parameters studied were age, number of years with erectile dysfunction (ED), diabetic history, hypertension, hyperlipidemia, smoking and alcohol abuse.
Patients were evaluated for erectile function by intracavernous pharmacological injection of 40mg papaverine. If good erection was achieved within 10 min and maintained for less than 30 min, the patient was considered as having ED due to venous leakage. All 28 patients underwent further testing by conventional DDU and DICC. Signs of corporal veno-occlusive dysfunction during DDU were (a) peak systolic velocity in dorsal vein greater than 10 ml [s.sup.-1]; (b) 30-50% increase in vein diameter; (c) change of dorsal vein blood flow into the opposite direction when Valsalva test was performed. DICC was commenced 5 min after intracavernous injection of 40 mg papaverine at an initial rate of infusion of 10 ml [min.sup.-1]. Then the infusion increased and reduced to determine the level of initiating erection and the level of maintaining erection. An infusion rate greater than 35 ml [min.sup.-1] to initiate erection, for greater than 30 ml [min.sup.-1] to maintain erection and a decrease of more than 50 cm water in corporeal pressure within 30 s following cessation of infusion were considered indicative of veno-occlusive dysfunction. All patients underwent further DICC with the aim to visualize the location of venous leakage from the corpora cavernosa. After intracavernosal injection of 40 mg papaverine, 60-80 ml of contrast media Omnipaque 150 diluted 1:2 with saline solution (total volume 40-60 ml) was infused to opacify the cavernous body. Frontal and bilateral 30[degrees] anterior oblique radiological views were taken to visualize the corpora cavernosa and the penile venous network.
MRI technique is based on intracavernous injection of paramagnetic contrast agent that contains gadolinium, after pharmacologically induced erection. Contrast enhancement is achieved by the gadolinium contrast agents in changing the chemical relaxation properties of extracellular fluid. It results in the reduced time of T1-relaxation and the increased signal intensity from the blood in special impulse sequences. Thus, an effect similar to angiography is obtained. Studies were performed using an MRI scanner 'Magnetom Symphony' (Siemens, Erlanger, Germany) with field strength of 1.5 T. A three dimensional/flash impulse sequence, developed for MRA with contrast enhancement, was used to make 1.5 mm thick slices in a sagittal plane.
The patients were informed and given adequate explanations for the details of the procedure to minimize any anxiety or fear during the investigation. Full rigid penile erection induced pharmacologically was achieved in all patients by administering of 40 mg papaverine for the complete cavernosal smooth muscle relaxation; thus, duration of this erectile status was adequate for performance of the MRI.
To standardize MRI testing results, two healthy men with good axial rigidity at intracavernosal injection test were examined. We recognize that it is impossible to compose a large control group due to ethical principles. In one case, we did not detect any venous leakage during MRI and in the second case visualized minimal traces of contrast media in the periprostatic plexus. We explain this observation as the variant of normal penile blood circulation during erection.
After achieving an erect penis, the first sequence of three dimensional/flash was carried out without contrast enhancement. Then 8-10 ml of contrast agent was introduced into one of the corpora cavernosa within 1 min. Sequential post-contrast measurements, 1-2 min later, were started in the series. After completion of measurements, a Syngo-MR program subtracted pre-contrast and post-contrast images automatically and built reconstructions based on maximum intensity projection on three mutually perpendicular planes. Contrast agents with active component molarities concentration of 0.5 (Magnevist, Schering AG, Berlin, Germany) and 1 (Gadovist 1.0, Schering AG) were used in the study. Nonparametric data, which was a rate of the venous leakage visualization defined by the both methods, were confirmed by specific criteria (z and [chi square]). For parametric data (duration of the both examinations) we used t-test.
The suspected diagnosis of corporal veno-occlusive dysfunction was diagnosed in 28 patients by DDU and DICC and venous leakage was confirmed and documented by these conventional methods in 21 of the 28 (75%) patients. A total of seven patients with mild ED by IIEF scores did not reveal clear radiological signs of venous leakage after they underwent DICC.
To establish that MRI visualizes penile hemodynamics, a MRI scan that was performed in two healthy men with no venous leakage is shown in Figure 1. MRI studies consistent with veno-occlusive dysfunction revealed various locations of pathologic venous leakage (Figures 2-7). This included visualization of distal draining veins in 9 patients (32%), proximal draining veins in 7 patients (25%) and mixed proximal and distal draining veins in 12 patients (43%). Furthermore, we could precisely visualize anatomic structures of the penis which were involved in venous leakage, including the deep dorsal vein, glans penis, corpus spongiosum, emissary veins, veins of the periprostatic plexus and deep draining veins. The groups of the patients and examination methods performed are presented in Tables 1 and 2. DICC did not reveal any significant venous leakage in seven patients with mild ED; however, venous leakage was identified by MRI (see Figures 8 and 9). Moreover, MRI provided additional information such as venous leakage type and location which cannot be documented with DICC (see Tables 3 and 4).
It should be noted that after the diagnosis with MRI, none of the patients experienced any complications (severe pain, allergy and priapism) except in two cases where minimal hematoma of penile cutis was noted in the site of injection. None of the patients experienced an anxiety or fear during the MRI throughout the time of the procedure. The limitations of the MRI are that the duration of MRI surpasses that of the conventional techniques (30 [+ or -] 5 min for MRI vs 15 [+ or -] 3 min for DICC; (P<0.001) and the high cost of paramagnetic contrasting medium (Magnevist, Gadovist) as compared to the medium used in DICC (Urographin).
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Hemodynamic testing of ED patients is performed to evaluate the integrity of the arterial and corporal veno-occlusive function during erection. Such information is critical for diagnosis, treatment and management of ED. This is more relevant when reconstructive surgical options, such as penile revascularization, or implantation of a penile prosthesis are considered. (8) Reconstructive procedures for venous leakage include surgical liation of the venous channels leaving the corpora (15,16) and radiological embolization of these venous channels. (17) Long-term success after venous surgery remains unsatisfactory. (15) Although the indications for penile revascularization are clear, it is still not known which patient, if any, will benefit from venous ligation and what diagnostic criteria are appropriate. (18) Meuleman et al. (18) reported that candidates for veno-restrictive surgery are men with anatomical abnormalities such as ectopic veins exiting the cavernous corpora or abnormal communications between the cavernosum and glans/spongiosum. From a diagnostic perspective, venous leakage of a minimum extent is not practically visualized by DIM If treatment for corporal veno-occlusive dysfunction is ever to become practical, safe and effective in the future, appropriate diagnostic studies are required. From our point of view, the introduction of MRI with contrast enhancement may improve the assessment of venous leakage visualization. Precise visualization of vein leakage and its three-dimensional reconstruction may assist in treatment planning in the rare cases where surgical treatment may be considered an option. On the contrary, if the significant venous leakage is identified, and pharmacologic vasoactive agents have proven unsuccessful, penile prosthesis insertion may be considered as the last option. An important positive factor in using MRI is that this method has limited radiation compared to traditional DIM On the other hand, MRI is expensive tool and the technique of injection of the contrast media during the procedure requires specialized staff and the time of the MRI procedure doubles that of DIM These limitations may significantly impact the use of MRI in sexual medicine clinics. This would place MRI as a second line hemodynamic diagnostic study in men with venogenic ED.
In summary, this preliminary report provides a proof of concept study in which MRI may become a diagnostic tool for assessing venous leakage in ED patients. Further studies to evaluate the utility of MRI in comparison with DICC are need. We believe that MRI with contrast enhancement will be a useful tool for the visualization venous leakage in ED patients and someday may become part of the clinical management algorithms of men with venous ED.
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The authors declare no source of funding. We are indebted to Professor Abdulmaged Traish, Boston University School of Medicine for his critical reading and editing of this manuscript.
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DG Kurbatov, YY Kuznetsky, SV Kitaev and VA Brusensky
Clinical Hospital #6 of Federal Medico-Biological Agency, Moscow, Russia
Correspondence: Dr DG Kurbatov, Clinical Hospital #6 of Federal Medico-Biological Agency, 23 Marshala Novikova st, Moscow 123098, Russia.
Received 25 June 2007; revised 20 July 2007; accepted 24 July 2007; published online 6 September 2007
Table 1 Patient characteristics and comorbidities Patient characteristics Parameters and comorbidities Mean age (range) 43.4 [+ or -] 7.2 (32-56) years Mean IIEF (range) EF 12.2 [+ or -] 2.6 (7-17) Severity of ED (a) Mild 7 Moderate 9 Severe 12 Comorbidities: Diabetes mellitus Three patients Arterial hypertension Two patients Hyperlipidemia, aterosclerotic Three patients cardiovascular disease BPH/LUTS Three patients Secondary hypogonadism Six patients Heavy smoking 11 patients Alcohol abuse Eight patients Abbreviations: BPH, benign prostatic hyperplasia; ED, erectile dysfunction; EF, erectile function; IIEF, International Index of Erectile Function, LUTS, lower urinary tract symptoms. aBased on the IIEF erectile function domain, where severe = 1-10, moderate = 11-16 and mild >17. Table 2 Hemodynamic diagnostic studies Method Number of Number of Total patients patients number with without of visualized visualized patients venous venous leakage leakage Dynamic infusion 21 7 28 pharmacocavernoso- graphy MRI 28 0 28 Abbreviation: MRI, magnetic resonance imaging. Table 3 Diagnostic values of irradiation methods in detection of venous leakage Method Sensitivity Sensitivity (%) (%) Dynamic infusion 72 93 pharmaco- cavernosography MRI 100 100 Method Positive Negative predictive predictive value (%) value (%) Dynamic infusion 98 29 pharmaco- cavernosography MRI 100 -- Abbreviation: MRI, magnetic resonance imaging. Table 4 Methods of venous leakage diagnosis evaluation Type of venous leakage Dynamic infusion MRI pharmacocavemosography (n = 28) (n = 28) Distal draining veins 8 9 only Proximal draining veins 5 7 only Mixed distal and 8 12 proximal draining veins No signs of venous 7 0 leakage Abbreviation: MRI, magnetic resonance imaging.