Advanced Ultrasound Techniques

Ellison Bentley, DVM, Diplomate ACVOUniversity of Wisconsin-Madison

School of Veterinary Medicine

High resolution ultrasound• Ultrasound biomicroscopy

(UBM) and high resolution ultrasound (HRUS)– Low power histology-like

view• Resolution-20-80µm

– 10MHz-300-400µm• Tissue penetration limited

to 5-10mm40MHz HRUS image canine

High resolution ultrasound• Clinical Uses: anterior

segment evaluation, uveal tumors, cysts, scleral and corneal disease, drainage angle, changes in these structures in disease

• Research: effect of drugs on anterior segment structures, pathophysiology of anterior segment diseases

HRUS(20MHz) image of canine eye

Cornea

IrisCB

Lens

Ciliary cleft

• HRUS correlates with histo

40MHZ

UBM vs HRUS

UBM• 50MHz-higher

resolution• Smaller field of view• Less penetration• Positioning critical• Sedation/anesthesia• Higher cost

HRUS• 20MHz - 40 MHz-lower

resolution• Larger field of view• Deeper penetration• Easier positioning• Topical anesthesia• Lower cost

UBM vs HRUS

50 MHz

10 MHz20

MHz

Courtesy C. Kendall, Innovative Imaging, Inc.

UBM vs HRUS

UBM image High resolution ultrasound image40MHz probe

• Not all probes created equal

50MHz

50MHz

20MHz

40MHz

Technique• Topical anesthetic• Genteal Gel/Optixcare• Superior and temporal quadrants easiest

– Ventral and nasal may require sedation

Probe position-longitudinal

Can label by clock hour

40MHz 12AX

Probe position-transverse

Note ciliary processes20MHz

40MHz 12T

Cornea

• Corneal thickness assessment

• Sequestrums-deeply pigmented lesions hyperechoic

• Deeper, faintly stained area not visible

• Contralateral eye: control

Sequestrum

Hyperechoic sequestrum‘Normal’ cornea=0.27

Normal contralateral eyeCorneal thickness=0.58mm

Corneal tumors

• Corneal tumors in horses– Sometimes difficult to assess depth

• Limbal melanomas with corneal extension in dogs

Hemangioma in a horse

Uvea

• Useful to differentiate tumors versus cysts• Useful to evaluate tumor extension • Useful to determine which patients are good

candidates for laser therapy for tumors; progression

• Can use to determine location of ciliary processes for cyclophotocoagulation

Uveal cysts

2 yr FS Golden retriever Note bilobed uveal cysts

Uveal cysts

10 yr old DSH referred for ciliary body tumor

17 year cat referred for ciliary body tumor

20MHz

20MHz

Feline cysts-COPLOW

• 15 eyes removed for suspected neoplasia

• 14/15=uveal cysts• 1/15-PIFMFeline cysts masquerading as neoplasia in catsFragola, Dubielzig, Bentley, Teixeira, VO 2018

Uveal tumors

4 yr MN mixed CNPre laser=0.80mm

Immediatepost laser=1.17mm

Uveal tumors

3 months post laser= 0.58 mm

15 months post laser=0.82 mm; re-lasered

Location of ciliary processes

• 8 yr Shiba Inu-primary glaucoma; candidate for gonioimplant, laser

• Location of ciliary body:– 5.31 mm superiorly– 4.77-5.02

inferiotemporal

Lens

• Useful to detect peripheral lens abnormalities

9 yr FS mixed breed, diabeticLIU more severe OS; HRUSperipheral lens capsule rupture,closed cleft

Iridocorneal angle

• Can examine ciliary cleft in greater detail• Can be useful in glaucoma cases, pre-op

cataract cases (?)• Maybe predict onset in ’good’ eye?

Typical glaucoma patient…

Iridocorneal angle

• Predictive value for onset of glaucoma?• Closed cleft at dx-6.5 mos• Open cleft at dx-22 mos

OD OS

• Ultrasound weakness=hyphemavs tumor

• Retinal detachment versus vitrealmembrane

Contrast-visualizing blood vessels• Doppler-detects

movement of blood and contrast agents

• Ocular movement=artifact

• Orbital cases• Labruyerre, Hartley,

et al JSAP 2011-contrast better than Doppler

Contrast ultrasound-seeing vessels

• Contrast agents-exogenous air or gas

• Specific agents: high molecular weight/low solubility gas microbubbles

Anesthesiology. 2004;101(3):614-619.

Contrast ultrasound-instruments

• Bubbles=scattered echoes

• Contrast agents-echogenic only at high doses; severe attenuation fundamental frequencies

Harmonic frequencies

• Fundamental-frequency-transmitted by probe

• Harmonic-multiples of transmitted

• 4 MHz transmitted– 2, 8, 12, 16 MHz

Pulse inversion imaging

• 2 waves-one inverted– Cancelled out=no signal

• Waves from contrast=signal

Contrast agent safety

• FDA-cardiac only• Anaphylactoid-2 dogs• 488 dogs/cats contrast

ultrasound vs 262 ultrasound alone– 0.2% (4 dogs)-vomiting

and syncope

Contrast disadvantage• Specialized machine required• Cost of contrast agent-$5/bottle

– 1 bottle/patientAgent Dosage Reference

Levovist 80 mg/kg Scharz et al. (2005) Rademacher et al. (2005)

Definity Dogs: <20kg, 0.1 mL, >20kg, 0.2 mL

O’Brien et al. (2004)

Optison Dogs: 0.5 mL Yamaya et al. (2002)Sonovue Dogs: 0.04-0.06 mL/kg

Dogs: <20kg, 0.5 mL, >20kg, 1.0mLDogs: 0.03 mL/kg

Nyman et al. (2005)O’Brien et al. (2004)Ohlerth et al. (2005)

J Ultrasound Med 21:299–307, 2002

90% divided by the number of frames, and thechange in video intensity was the increase frombaseline. The baseline was defined as the aver-age of 10 frames just before the rising phase ofthe curve. The calculated values from the curvesclosely correlate with tissue perfusion.

We checked the fundus after the examinationand compared the findings with those beforeexamination to confirm the safety of thismethod.

For statistical analyses, data were expressed asmeans. Correlation was performed by a Wilcoxonnonparametric rank sum test with SPSS version10 software (SPSS Inc, Chicago, IL). For differ-ences, P < .05 was considered significant.

ResultsWith the ultrasonographic contrast mediumand low-MI harmonic imaging, the ultrasono-graphic intensity of all orbital tissues increasedexcept in the tissues known to have no bloodflow in intact eyes. Contrast-enhanced tissueswere identified by comparison with the 10-MHzfundamental images obtained before contrast-enhanced imaging. Contrast enhancement firstappeared at the retrobulbar arteries, followedby the uveal tissue, extraocular muscles, andfinally the optic nerve. There was no change inthe vitreous humor, because we know that thenormal vitreous humor has no blood vessel.This enhancement pattern was reproducible(Fig. 5), and the brightness of the avascularregion showed little change, as expected (Fig. 6).

When the harmonic mode was switched to thefundamental mode, video intensities of theuvea, vessels, and muscles were diminished,and intensities in the remaining tissuesremained unchanged (Fig. 7).

Figure 8A illustrates the relationship of timeversus signal intensity in the uvea of a healthyeye, and Figure 8B shows the relationships inan eye with impaired blood flow. Table 1depicts the values of the rise-time slope and thechange in video intensity in both groups. Thesevalues for the uvea are significantly greater in

J Ultrasound Med 21:299–307, 2002 303

Hirokawa et al

Figure 4. Fundal ICG angiographic image of the same eye as inFigure 3 showing a defect in the avascular area of the fundus. Inthis method, near-infrared light is used, which is much more effi-cient in penetrating pigmented tissues of the fundus comparedwith the wavelength of visible rays. Therefore, this techniqueseems to be more proper for showing choroidal blood flow.

Figure 5. Harmonic ultrasonography of the normal transverse eye. A, Just before injection of the contrast agent. B, Just after the injection. Immediatelythe video intensity of vessels and uvea was instantly enhanced.

A B

Pre contrast Post contrast

with this finding. Detection of the avascular areain the uvea especially showed excellent correla-tion with fundal angiography. A combination ofhigh-frequency harmonic imaging with a con-trast agent insonating at a low MI has achievedsuch excellent resolution and reproducibility.7,15

An additional factor for the favorable results isthat the target tissues were near the probe, andsignals from bubbles were efficiently received.However, variations in quantitative signal inten-sity were observed.

Nevertheless, our study is still limited by sever-al factors. First, there is no reference standard forperfusion examination in orbital organs as forthe myocardial scintigram in the heart. The fun-dal ICG angiography used as a control for perfu-sion in our study is like fluoroscopy with aniodine agent and provides little information ontissue viability.4 Also, the microbubble harmonicphenomenon at 5 MHz and higher has not yetbeen examined adequately. In our study, a simplein vitro experiment was performed only to con-firm resonance and insonation. Taking intoaccount the properties of the shell wall and bub-ble size, further studies are necessary and shouldfocus on biophysical problems.16 Another issue isthat information on blood flow direction andvelocity is not provided by this method. In thisaspect, it is very different from color Dopplerimaging. Some ophthalmologic facilities usecolor Doppler imaging for assessment of retro-bulbar hemodynamics by using the resistanceindex. However, this index is not highly repro-ducible, because it tends to be affected by thepassage of blood vessels. Furthermore, an MI

value greater than the FDA guideline is used forclear measurement. The major objective of ourexamination was to visualize perfusion, andblood flow direction and velocity are expressedmore indirectly by color Doppler imaging thanby our method. Furthermore, our method com-plies with the FDA guideline, and the qualitativedata have high intrasubject and intersubjectreproducibility.

Contrast-enhanced echography has propertiesthat can be exploited to provide informationrelated to tissue perfusion. Our method has thepotential for expansion to clinical ophthalmicpractice for investigation of complex etiologiesof diseases such as glaucoma and age-relatedmacular degeneration, especially glaucoma, theprevalence of which is 3% of all Americans 40years and older,1 some patients also havingischemic optic neuropathy, which is curable byneurosurgery.17 Nowadays, this disease isdiagnosed by traditional ophthalmologicexaminations that provide little retrobulbarhemodynamics assessment. Our method mayprovide some useful information for deter-mining indications for neurosurgery.

In this study, we have determined somerequirements for an ideal ultrasonographic con-trast agent for visualizing orbital perfusion. Anagent that is active at a low MI is preferable, andbubble destruction should occur at an MI oflower than 0.24 for quantitative measurement.There is obviously a need to develop a highly sen-sitive bubble detection method, such as higher-frequency harmonic imaging at a low MI,without compromising penetration.

306 J Ultrasound Med 21:299–307, 2002

Contrast-Enhanced Harmonic Ultrasonography of Uveal Perfusion

Figure 9. Fundus before (A) and after (B) ultrasonographic examination. No change is evident after the examination.

A B

Research• Would cavitation of contrast bubbles

cause tissue damage in the eye?

Pre contrast Post contrast

Constrast enhanced ultrasound• Good for:

– Retinal detachment• Differentiating retinal detachment vs vitreal membrane

– Differentiation of solid tumor vs hemorrhage or exudate

• Less helpful with diffuse tumors in tissues that light up anyway (ie no tissue expansion)

• Bad for:– Masses with lots of necrosis– Small tumors– Retinal detachment with devitalized retina

12AX

20MHz at 6AX

Thank you Gill McLellan!!

Contrast

Iridociliary adenoma

Contrast

3D ultrasound

• Pre-natal imaging• 2D computerized

reconstruction• Limited ophtho reports• Movement artifact

3D ultrasound

3D

3D

Thanks to:COPLOW

UW Ophthalmology:

Erin ScottAlly Gosling

Andrew LewinPaul Miller

Gillian McLellanKim ShermanBecky Telle

UW Radiology:Ken Waller

Fern Delaney