Doppler Blood FlowAnalysis of Erecti leFunction: Who, When,and How

Timothy J. LeRoy, MD, Gregory A. Broderick, MD*

KEYWORDS

� Erectile dysfunction � Penile Doppler sonography� Ultrasonography � Peyronie’s disease

OVERVIEW

Since the introduction of several effective oraltreatments for erectile dysfunction (ED), primarycare physicians and midlevel providers managemost patients wishing treatment of male sexualdysfunction. ED is defined as the consistent orrecurrent inability to attain and/or maintain penileerection sufficient for sexual performance.1 EDconstitutes an evolving public health concern.Studies from the 1990s estimated that half ofmen older than 40 years had ED.2 Public aware-ness, pharmaceutical marketing, and new areasof research, such as cancer survivorship, arealso increasing. In aggregate, this research andawareness is increasing the demand for treatmentto the primary provider. Failure or poor efficacy offirst-line treatments often leads to specialtyreferral. Other reasons for specialty referral maybe trauma, uncertainty of diagnoses, or simply,the wish of the patient or provider.

Broadly categorized, there are 3 types of ED:neurogenic, psychogenic, and vasculogenic.Neurogenic and psychogenic causes are dis-cussed by Altof and Needle elsewhere in thisissue. Vasculogenic causes can be arterial, ve-noocclusive, or some combination of the two. Vas-culogenic ED may account for up to 60% to 80%of all cases reported.3

There has been considerable research into diag-nostic techniques over the past few decades.Without invasive testing, the urologist was limited

Disclosure statement: The authors have nothing to discloDepartment of Urology, Mayo Clinic Florida, 4500 San P* Corresponding author.E-mail address: Broderick.gregory@mayo.edu

Urol Clin N Am 38 (2011) 147–154doi:10.1016/j.ucl.2011.03.0030094-0143/11/$ – see front matter � 2011 Elsevier Inc. All

to inferences made from physical examinationand patient-based questionnaires. More datawere often required to make solid clinical andsurgical decisions. This requirement of dataprompted several different types of investigations.The first-line diagnostic test for vasculogenic EDhas been combined intracavernous injection andstimulation (CIS) and direct assessment by anobserver.4 This test is used to bypass both neuro-logic and hormonal influences and allow theprovider to directly evaluate the vascular statusof the penis. A normal response from CIS is asso-ciated with appropriate venous occlusion. False-negative results are found in as many as 20% ofpatients with intermediate arterial inflow. False-positive result could also commonly occur.

If more testing is thought to be needed or anoperative intervention is being considered, suchas for Peyronie’s disease or for pelvic trauma,a second-line study is warranted. The pharmaco-penile Doppler ultrasonography (PDDU) is a diag-nostic modality useful in determining the subtypeof vasculogenic ED as well as the magnitude ofits severity. PDDU involves injecting a vasoactivepenile stimulant followed by genital self-stimulation, audiovisual stimulation, or in somecases, repeat injection during which blood flow isassessed by color duplex Doppler ultrasonog-raphy. This procedure allows for both a direct anda quantifiable evaluation of ED. Ultrasonographyis also able to provide information on the

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underlying soft tissue abnormalities such as aPeyr-onie’s plaque.

PENILE ANATOMY

Three cylindrical structures, the corpus spongio-sum, ventrally containing the urethra, and thepaired corpora cavernosa, form the penis. Thecorpora cavernosa are covered by a 2-layer tunicawith outer longitudinal fibers and inner circularfibers. There are also fibrous struts that help addsupport to the erect penis. The intracavernosalseptum incompletely divides the 2 cylinders. Clin-ically, this anatomy is advantageous because onlya single injection to the corporal body is required.The medication will circulate to the contralateralside. The tunica albuginea itself is also coveredwith a more superficial Buck fascia and a looseconnective tissue and skin (Fig. 1). On ultrasonog-raphy, the corpora cavernosa appears hypoechoicand encased in a hyperechoic tunica.Arterial supply to the penis is from the branches

of the common penile artery, which is the directcontinuation of the internal pudendal artery bilater-ally. This artery branches into 3 named arteries.The cavernosal artery pierces the corporal bodyand travels in the center of the erectile tissue.These arteries are evaluated during the ultrasono-graphic study as discussed later. The bulboure-thral artery enters the spongiosum superiorly and

Fig. 1. Cross section of the penis demonstrating the visua

supplies the urethra, the spongiosum, and theglans penis. The third artery is the dorsal arteryof the penis that courses between the dorsal veinand penile nerves. It gives off branches to thecavernous bodies and circumferential branchesto the spongiosum. As with much of the pelvicvasculature, considerable variations have beenfound in the arterial supply to the penis.5,6 On ultra-sonography, the arteries can be found in severalimaging planes and are easily seen as brightparallel lines because the arterial walls are hyper-echoic (Fig. 2). The venous drainage of the corporabegin with the intersinusoidal and subtunicalvenous plexuses. This venous drainage continuesto the emissary veins and then to larger channelssuch as the dorsal vein of the penis. The venousfunction in ED is described later.

PHYSIOLOGY OF ERECTION

In a flaccid state, the subtunical and intersinusoi-dal veins freely flow to the emissary veins. Thearterioles and sinusoids maintain a high restingtone, which limits the inflow into the corpora.When combined, these yield a flaccid penis. Afterappropriate neural stimulation, a cascade ofneurotransmitters, such as nitric oxide, affect thevascular supply to the penis. This starts with relax-ation of the smooth muscle in the cavernosalarteries and then proceeds to the sinusoids. This

l anatomy noted on a typical study.

Fig. 2. Acavernous artery is seen in this sagittal ultraso-nography. Theappearanceof thearterialwalls is consis-tentwitharthrosclerosis and/or calcification. RCA, rightcavernous artery.

Doppler Blood Flow Analysis of Erectile Function 149

relaxation promotes a high inflow to the corporalbodies. Tumescence continues as the sinusoidsfill with blood and begin to engorge. As the tunicaelongates and expands, it begins to occlude theemissary veins between the inner circular and

Fig. 3. Physiology of erection revealing the changes in thelature. (A) The normal anatomy and physiology in the erethe flaccid phallus.

outer longitudinal layers described earlier. (Fig. 3)The occlusion propagates the erection becauseinflow is high and vascular outflow is at a minimum.Eventually, the intracorporal pressure increases tosystemic levels and the inflow becomes reducedas well. Initially, the glans penis and corpora spon-giosum react similarly in regard to flow. The majordifference is the lack of tunical coverings and thusminimal venous occlusion. These structurescontinue to have high arterial inflow and functionsimilar to an arteriovenous shunt. Just as tumes-cence proceeds step-wise, detumescence doesso as well, with several separate stages proceed-ing according to penile pressure as the penisreturns to its normal state.

PATIENT SELECTION

As with most diagnostic interventions, the patientselection process begins only after a satisfactoryevaluation has been performed. A full patienthistory should be obtained, including a medical,surgical, sexual, and psychosocial history. Theuse of a patient self-assessment such as the Inter-national Index of Erectile Function or the SexualHealth Inventory for Men is also helpful in the

corporal smooth muscle and the accompanying vascu-ct phallus, (B) the normal anatomy and physiology in

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standard evaluation. Given the considerablepatient, and potentially even physician awkward-ness of this type of interaction, the authors recom-mend an attitude of comfort and adaptabilitythroughout the evaluation process.7 Physicalexamination should include a broad screening formedical comorbid conditions relevant to ED,such as body habitus and blood pressuremeasurements. Urologic evaluation may revealphysical findings such as Peyronie’s plaques,and neurologic evaluation may yield clues toneurogenic causes including presence of the bul-bocavernosus reflex or peripheral neuropathy sug-gesting diabetes. Laboratory studies to identify orconfirm a specific cause, such as hypogonadism,may be used as appropriate.Many patients have an obvious and often severe

cause of ED, such as Peyronie’s disease, pelvicsurgery, or metabolic syndrome. Another largesubset of patients would have tried and failedoral treatments with phosphodiesterase 5 inhibi-tors. Further testing to confirm the cause is notmandatory for the urologist. First and foremost,the provider should review the medications triedand their doses to ensure that first-line trials havebeen appropriate. The provider may then pursueother empirical treatments such as intracavernosalinjections, but the patient should have an option ofundergoing more definitive studies. Some patientswho have undergone CIS report that even thoughthey had an appropriate response in the clinic, itdoes not correlate with their “home” experience.This report might be an indication of venous leak,and PDDU may be helpful to better understandthe cause of the patient’s ED.4 Another indicationfor PDDU is operative planning. If, for example,the urologist is deciding between plaque excisionand grafting and a penile implant for Peyronie’sdisease, a quantifiable examination of penile bloodflow may provide the data needed for the decision.

TECHNIQUE OF PENILE DOPPLERULTRASONOGRAPHY

As with any invasive procedure, a proper informedconsent should be undertaken with the patient out-lining the purpose, alternatives, risks, and benefitsof the testing process. The examination roomshould be comfortable, safe from intrusion anddistraction. False-positive test results (a partialerection when there is no underlying vascularabnormality) may ensue secondary to patientanxiety, needle phobia, and/or inadequate medi-cation dosage. Although penile sonography isnoninvasive to the patient, intracavernous injec-tions (ICI) have morbidity that both the examinerand patient should be informed of. It is reported

that 1 in 5 neurologically intact men complain ofan ache in the penis after prostaglandin E1 injec-tions. Prolonged erection is another well-knownrisk and must be pharmacologically reversed withsubsequent injections to avoid priapism and itssubsequent morbidity. Equipment neededincludes a 5/8-in needle (27–29 gauge) and syringefor injection and the vasoactive medication chosenby the examiner for the study. A high-resolutionultrasonographic probe (7–10 MHz) is able toperform real-time ultrasonography and colorpulsed Doppler. This technique allows the exam-iner to evaluate penile blood flow changesthroughout the various phases of erection. Incolor-coded duplex sonography, the direction ofblood flow is designated with red (toward theprobe) or blue (away from the probe), making theidentification of the small cavernous vessels andrecording of blood flow easier.8,9

Attempts have been made to lessen the inva-siveness of PDDU by substituting an oral medica-tion such as sildenafil for injectable medications.These studies did show an increase in the peakflow velocities that were comparable to thoseseen with ICI, but the time frame was considerablylonger. Testing may begin in 1 to 20 minutes withinjectables versus in 30 to 90 minutes after anoral medication.10 Other similar studies foundthat oral medications did not provide as strongan efficacy or any response when compared withinjectable medications.11,12 Further complicatingoral medications such as sildenafil is that oftenthe patient selected for PDDU has already hadpoor efficacy with that treatment type.An example protocol of study would include an

injection of 10 mg of prostaglandin E1 (alprostadil).Direct pressure may be applied to the injection sitefor 2 to 3 minutes to prevent hematoma formation.If the examiner suspects a robust response giventhe patient’s history and physical examination,this dose may be decreased by half. If necessary,the dose may be escalated up to 20 mg. This is onlyone of several possible medication protocols thathave been described. Other agents that havebeen used include papaverine (7.5–60 mg), papav-erine with the addition of phentolamine (0.1–1 mg),and papaverine 1 phentolamine 1 alprostadil.Some protocols use redosing of alprostadil,10 mg, 1 phentolamine, 1 mg, 1 papaverine,30 mg, (Trimix) to help predict arterial dysfunctionif the initial dose of alprostadil fails. This protocolhas been shown to have a higher risk of prolongederections and priapism (10% with Trimix vs 1%with alprostadil alone).13 The initial flows shouldbe measured 5 to 10 minutes after injection.Some investigators recommend measurementsevery 5 minutes for the first 20 to 30 minutes, but

Doppler Blood Flow Analysis of Erectile Function 151

this is often not practical in a busy practice. It is notunusual for the initial response time to be changedbased on the patient’s mental state and medicalconditions. For example, a delayed response canbe found in the hypertensive patient as well asthe anxious patient. A rapid and robust responsecan be expected in the young man with psycho-genic ED and patients with a neurogenic cause(including after prostatectomy and colorectalsurgery). The examiner should record the erectionhardness and correlate this with the PDDUmeasurements. A recent validated scale, the Erec-tion Hardness Score (scale 1–4) can be used tostandardize responses.14 As first described by Do-natucci and Lue,4 the combination of injection plusmanual self-stimulation leads to higher rates ofrigid erections compared with injection alone. Assuch, the patient should be reexamined afterself-stimulation. Other investigators suggestrepeat pharmacostimulation as an adjuvant ifself-stimulation is not preformed.15 When there isfull tumescence (or best achieved rigidity), gray-scale imaging for the presence of nonvascularabnormalities such as plaques and fibrosis shouldbe performed and noted. Doppler evaluationsshould include samples at the penoscrotal junctionfor the evaluation of blood flow at intervalsdescribed earlier and any physical deformity noted(such as a Peyronie’s plaque). Evaluating theblood flow at the base of the penis limits the effectof penile pressure on arterial inflow.15 Both arteriesshould be evaluated in a typical study.

At then end of the testing period, it is importantto ensure a complete detumescence. The patientshould not leave the office until the penis returns

Fig. 4. The normal Doppler waveform changes over timethe waveform initially shows a diastolic flow. This then st

to a normally flaccid state. This will sometimesrequire injecting a diluted phenylephrine (ana-adrenergic agonist) solution of 200 mg /mL, given1 mL every 3 to 5 minutes until detumescence. Thepatient should bemonitored for symptoms such asacute hypertension, tachycardia, arrhythmias, andpalpitations. Some providers choose to usea cardiac monitor during this process.

NORMAL STUDY

The PDDU should be preformed as describedearlier. Measurements and rigidity should berecorded. Fig. 4 demonstrates the normal Dopplerwaveform of a PDDU over time. Initially, the penileflow is elevated, both systolic and diastolic,because of smooth muscle relaxation. As thepenile pressure increases the diastolic flowdecreases and eventually reverses direction. Atpeak pressures, the arterial flow is dampenedand no diastolic flow is noted. There are severalpossible parameters that might be measured, butthe most common ones are peak systolic velocity(PSV), arterial diameter, end-diastolic velocity(EDV), and resistive index (RI). These variablesare described in context with the pathologic condi-tion they best elucidate. Performing an evaluationas described earlier should allow the examiner tounderstand the cause of a vasculogenic ED, ifpresent in the patient.

ARTERIAL INSUFFICIENCY

Sufficient arterial inflow is of paramount impor-tance to the study because without it, adequate

in the normal subject. As the penile pressure increasesops and even reverses direction. B/P, blood pressure.

Fig. 6. This PDDU shows sufficient arterial inflow at51.4 cm/s poststimulation but an RI consistent withCVOD. A/B, points A & B; ACC, acceleration index;ET, elapsed time; RCA, right cavernous artery.

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erectile rigidity is unlikely to be obtained. Inflow isdirectly related to both arterial diameter as well asblood flow velocity. Whereas diameter can beuseful, it is many variables such as location ofexamination (distal vs proximal), compressionwith the probe, and normal anatomic differencesthat make it difficult to use arterial inflow as thesole standard. The finding typically used is thePSV. PSV represents the highest recoded bloodflow in the artery during systole. In the historicalliterature, in patients with abnormal pudendal arte-riography, PSV less than 25 cm/s has a sensitivityof 100% and a specificity of 95%.16 Severe unilat-eral cavernous arterial insufficiencies (AIs) aremanifested by an asymmetry of PSV greater than10 cm/s from the contralateral side. Many investi-gators conclude that a normal PSV should begreater than 35 cm/s. An example of a Dopplerwaveform of AI is shown in Fig. 5.

VENOOCCLUSIVE DYSFUNCTION OR VENOUSLEAKAGE

The trapping of bloodwithin the corpora cavernouslimits the venous outflow and is necessary fortumescence to occur. Cavernous venous occlu-sive disease (CVOD) is defined as the inability toachieve and maintain adequate erections despiteappropriate arterial inflow. OnPDDU, if theDopplerwaveform continues tomanifest high systolic flowsand persistent EDV greater than 5 to 7 cm/s, thepatient is considered to have CVOD. As seen inFig. 4, the only time one expects to see elevateddiastolic flow is at the beginning of tumescence.A continually high EDV is typically evident inCVOD. EDV alone looses specificity for venousleakage if it is associated with AI.17 As such,

Fig. 5. PDDU showing a peak PSV of 16.0 cm/s post-stimulation revealing that the patient has arterialinsufficiency. A/B, points A & B; ACC, accelerationindex; ET, elapsed time; RCA, right cavernous artery.

many investigators include another value thattakes PSV into account. This value is the RI. Theformula for RI is as follows:

RI 5 (PSV � EDV)/PSV

As the penile pressure equals or exceeds the dia-stolic pressure, the diastolic flow in the corporaapproaches zero and the value for RI approaches1. During tumescence as well as in partial erec-tions, the diastolic flow remains and the RI valueis less than 1.0. Naroda and colleagues18concluded that an RI of less than 0.75 predictsCVOD in nearly 95% of patients and that an RIgreater than 0.9 to 1 is normal. RI is typically re-corded at the 20-minute mark of the study. Fig. 6shows the typical waveform noted in CVOD.

Fig. 7. Doppler ultrasonography of a Peyronie’s pla-que. The plaque often manifests as a hyperechoic toisoechoic finding with through shadowing.

Fig. 8. PDDU of an arteriolar-sinusoidal fistula as is seen in nonischemic priapism. (A) PDDU waveform, note theelements of both a high PSV (in this study 40 cm/s) and elevated diastolic flow. (B) Color Doppler view over thefistula showing high flows of the left cavernous artery (LT CAV ART). RT CAV ART, right cavernous artery.

Doppler Blood Flow Analysis of Erectile Function 153

COMBINED DISEASE

As expected, combined disease manifestsfeatures of both AI and CVOD. The extent ofeach component may not be as severe whenpresent in combination. The typical findingsinclude a lower PSV, greater than 25 cm/s butnot higher than 35 cm/s. In addition to this finding,there will be evidence of CVOD. As discussedearlier, the specificity of EDV is blunted in the pres-ence of low arterial inflow. Therefore, the authorsuse RI and expect to see a value less than 0.9 ina combined disease picture.

PEYRONIE’S DISEASE

Peyronie’s disease is a male sexual disorder thatmay be associated with ED and pain on erection.It is a condition of the tunica albuginea character-ized by the formation of plaques of fibrous tissuethat results in various severities of penile curvature.The authors do not recommend PDDU as a first-line evaluation of Peyronie’s disease. A significantproportion of patients with this condition neverrequire medical or surgical intervention. Thediscussion of the cause andmedical/surgical inter-ventions in Peyronie’s disease is outside the scopeof this discussion. However, if there is significantED or severe curvature precluding sexual inter-course, the PDDU can be invaluable for surgicalplanning and patient counseling. Plaque lengthand characteristics can be readily demonstratedon Doppler ultrasonography. The PDDU is per-formed as described for the normal study. Thepharmacologically produced erection also givesthe examiner an idea of the severity and directionof penile curvature during tumescence. These

plaques often manifest as hyperechoic or isoe-choic lesions with through shadowing (Fig. 7). Acareful examination of the patient’s erectile qualityis also paramount because it can determine if thepatient is ultimately a candidate for a penile implantor one of the various incision/plication/graftingtechniques available.

PRIAPISM

Priapism is defined as a full or partial erection thatcontinues more that 4 hours beyond sexual stimu-lation or is unrelated to sexual stimulation. The 2broad categories are ischemic (low flow, venooc-clusive) and nonischemic (high flow, arterial) priap-ism. The dysregulated arterial inflows with orwithout a fistula can best be distinguished froma persistent ischemic priapism with PDDU. In thesetting of priapism, no injectable medicationsshould be used as part of the study. Dopplerexamination should include the cavernosal arteriesfrom the base of the corpora (ie, below the peno-scrotal junction) proceeding distally in an attemptto find a potential fistula. On PDDU, an ischemicpriapism simply shows no or very minimal arterialflow through the corpora. In high flow priapism,the examiner often finds a high PSV consistentwith increased arterial inflow. There is oftena high diastolic flow accompanying this observa-tion if examining the arteriolar-sinusoidal fistula(Fig. 8).

SUMMARY

In the appropriately selected patient, PDDU can beextremely valuable to the urology practitioner. Useof PDDU does require an understanding of the

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relevant penile anatomy and physiology of erec-tion as well as their clinical correlations to ED. Italso requires that the practitioner have access tothe Doppler equipment and pharmacotherapy forinjection. Following the steps outlined in this articleto perform the study, and by applying the basicunderstanding of the main vascular causes ofED, PDDU can be used to diagnose and guidethe patient and practitioner to the best treatmentoptions.

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