Measurement of equine laminar blood flow and vascular permeability by use of dynamic contrast-enhanced computed tomography

E. Freya Kruger Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Sarah M. Puchalski Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Rachel E. Pollard Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Larry D. Galuppo Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.

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William J. Hornof Eklin Medical Systems Inc, 568 Weddell Dr, Ste 1, Sunnyvale, CA 94089.

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Erik R. Wisner Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.

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DOI:
https://doi.org/10.2460/ajvr.69.3.371
Volume/Issue:
Volume 69: Issue 3
Online Publication Date:
01 Mar 2008
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Abstract

Objective—To define the reference range for laminar blood flow (BF) and vascular permeability (VPM) in horses without laminitis by use of dynamic contrast-enhanced computed tomography (CT).

Animals—9 adult horses that were not lame and had no abnormalities of the laminae or phalanges detectable via radiographic examination.

Procedures—Each horse was anesthetized by use of a routine protocol. Horses were placed in right or left lateral recumbency with the dependent forelimb in the CT gantry; only 1 limb of each horse was scanned. Serial 10-mm collimated transverse CT images were acquired at the same location every other second for 90 seconds during infusion of ionic, iodinated contrast medium. Custom software was used to estimate BF, VPM, and fractional vascular volume (FVV) in the dorsal, dorsomedial, and dorsolateral laminar regions.

Results—Among the 9 horses' forelimbs, mean ± SD dorsal laminar BF was 0.43 ± 0.21 mL•min−1•mL−1. Mean dorsomedial and dorsolateral laminar BFs were 0.26 ± 0.16 mL•min−1•mL−1 and 0.24 ± 0.16 mL•min−1•mL−1, respectively. Mean dorsal laminar VPM was 0.09 ± 0.03 mL•min−1•mL−1. Mean dorsomedial and dorsolateral laminar VPMs were 0.16 ± 0.06 mL•min−1•mL−1 and 0.12 ± 0.06 mL•min−1•mL−1, respectively. Mean dorsal laminar FVV was 0.63 ± 0.20 and dorsomedial and dorsolateral laminar FVV were 0.37 ± 0.14 and 0.34 ± 0.17, respectively.

Conclusions and Clinical Relevance—In horses, laminar BF, VPM, and FVV can be non-invasively measured by use of dynamic contrast-enhanced CT.

Abstract

Objective—To define the reference range for laminar blood flow (BF) and vascular permeability (VPM) in horses without laminitis by use of dynamic contrast-enhanced computed tomography (CT).

Animals—9 adult horses that were not lame and had no abnormalities of the laminae or phalanges detectable via radiographic examination.

Procedures—Each horse was anesthetized by use of a routine protocol. Horses were placed in right or left lateral recumbency with the dependent forelimb in the CT gantry; only 1 limb of each horse was scanned. Serial 10-mm collimated transverse CT images were acquired at the same location every other second for 90 seconds during infusion of ionic, iodinated contrast medium. Custom software was used to estimate BF, VPM, and fractional vascular volume (FVV) in the dorsal, dorsomedial, and dorsolateral laminar regions.

Results—Among the 9 horses' forelimbs, mean ± SD dorsal laminar BF was 0.43 ± 0.21 mL•min−1•mL−1. Mean dorsomedial and dorsolateral laminar BFs were 0.26 ± 0.16 mL•min−1•mL−1 and 0.24 ± 0.16 mL•min−1•mL−1, respectively. Mean dorsal laminar VPM was 0.09 ± 0.03 mL•min−1•mL−1. Mean dorsomedial and dorsolateral laminar VPMs were 0.16 ± 0.06 mL•min−1•mL−1 and 0.12 ± 0.06 mL•min−1•mL−1, respectively. Mean dorsal laminar FVV was 0.63 ± 0.20 and dorsomedial and dorsolateral laminar FVV were 0.37 ± 0.14 and 0.34 ± 0.17, respectively.

Conclusions and Clinical Relevance—In horses, laminar BF, VPM, and FVV can be non-invasively measured by use of dynamic contrast-enhanced CT.

Laminitis in horses is associated with many different systemic diseases and some biomechanical insults.1,2 Although the term laminitis implies inflammation of the laminae, the disease is much more complex, encompassing ischemia, necrosis, and permanent morphologic damage to the interdigitating system of dermal and epidermal laminae in the hoof.3–7 Unchecked, laminitis leads to separation of the third phalanx from the hoof capsule, displacement of the bone, long-term lameness, and frequently euthanasia.1,2,8 Laminitis research has pointed toward 2 broad theories to explain the pathophysiologic processes. The enzymatic theory proposes that proteolytic destruction occurs at the level of the basement membrane, whereas the vascular theory proposes that the primary injury occurs to the microvasculature leading to initiation and propagation of the disease.3,9-14 Histopathologic changes in the digital laminae that are associated with laminitis have been reported as consistent with tissue ischemia and reperfusion injury.4–6,9

In horses with naturally occurring or experimentally induced laminitis, alteration in BF has been detected by use of a variety of different techniques. Thermography provides an indirect estimate of BF through evaluation of the hoof surface temperature.15 Laser Doppler flowmetry16,17 and Doppler ultrasono-graphy18,19 provide estimates of total BF at a region of the coronary band or through the digital arteries, respectively, whereas venography20 provides a qualitative assessment of blood distribution. Nuclear scintigraphy provides a more quantitative assessment that can be used to evaluate laminar regions.21,22 However, both venography and nuclear scintigraphy provide planar images wherein superimposition can limit the evaluation of anatomic detail. The measurement of VPM has been less commonly performed; we are aware of only 1 study23 in which lymphatic flow was used as an indirect measure of VPM.

Dynamic contrast-enhanced CT is a technique that capitalizes on the excellent anatomic detail and rapid acquisition time of CT. Helical CT scanners are able to generate a series of thin, cross-sectional images in a single anatomic plane, resulting in a near real-time assessment of iodinated contrast agent as it flows into the region. The iodine concentration in tissue is linearly related to the recorded change in HUs; therefore, these data, plotted over time, can be used to estimate regional blood flow and VPM through mathematical analysis.24–26 These DCE-CT measurements have been validated by use of radioactive microspheres in normal, tumor-infiltrated, and ischemic brain tissue of rabbits.24,27 For the assessment of peripheral soft tissue tumors in rodents, DCE-CT estimates of BF and VPM have also compared favorably with values determined by use of gold standard techniques.26

The purpose of the study of this report was to define the reference range for laminar BF and VPM in horses without laminitis by use of an established and validated DCE-CT technique24,26 that had been modified for application in horses.

Materials and Methods

Horses—Nine university-owned horses were evaluated at the University of California, Davis, Veterinary Medical Teaching Hospital. The horses had no signs of clinical lameness and no evidence of laminitis was detected on complete radiographic examination of the distal portion of the forelimb. The institutional animal care and use committee approved the experimental protocols used in the study.

Anesthesia and catheterization—For each horse, xylazine hydrochloride (0.3 to 0.5 mg/kg, IV) and butorphanol tartrate (0.01 mg/kg, IV) were administered for sedation and analgesia. Anesthesia was induced with guaifenesin (100 mg/kg, IV) and ketamine hydrochloride (2.2 mg/kg, IV) and maintained with isoflurane and oxygen. For each horse, ventilation was provided for the duration of anesthesia.

Each horse was positioned in either right or left lateral recumbency with the dependent forelimb extended within the gantry of the CT unit. Only 1 limb of each horse was scanned, and use of the right and left forelimbs was alternated among the 9 horses. After positioning, the skin over the median or medial palmar artery of the dependent limb was clipped and aseptically prepared for catheter insertion by use of a technique previously described.28 An 18-gauge, 1.88-inch (1.8 × 48-mm) catheter was inserted with ultrasound guidance. The catheter was affixed to the skin with 2-0 polypropylene suture; a 70-cm pressure injector extension set was attached to connect the catheter to a continuous infusion pump.a Fiducial markers consisting of 3 aluminum bars were affixed to the outer surfaces of the hoof. The fiducial markers were used to evaluate and correct for any motion that occurred during the scan. After acquisition of the described imaging sequences, the catheter was removed from the artery, the limb was bandaged, and the horse was allowed to recover unassisted from anesthesia. All horses were housed in the hospital for 24 hours and monitored for complications related to the catheterization (heat, signs of pain, swelling, or changes in digital pulse quality) or anesthesia (alterations in rectal temperature, pulse, or respiration).

Data acquisition—A single detector row, helical CT scannerb was used for image acquisition. Lateromedial and dorsopalmar scout images were acquired initially. An initial imaging sequence of 5-mm collimated contiguous images from the middle of the first phalanx to the distal extent of the third phalanx was performed. From these scans, a location was identified that included the deep digital flexor tendon, collateral ligaments of the distal interphalangeal joint, and the laminae. Each horse was hyperventilated by use of a positive pressure ventilator, and then the ventilator was turned off for the duration of the contrast-enhanced scanning procedure, thereby inducing a single breath-hold for the image acquisition. A 10-mm collimated image was acquired at the chosen location every other second for 90 seconds starting 5 seconds prior to contrast medium injection. Each individual image was acquired over approximately 0.8 seconds, and 45 images were obtained. Ionic iodinated contrast mediumc (400 mg of iodine/mL) diluted 1:1 in physiologic saline (0.9% NaCl) solution was administered through the catheter in the medial palmar artery and controlled with an automated pump at 3 mL/s for 30 seconds (total volume administered, 90 mL). Computed tomographic tube output variables were 120 kVp and 150 mA, the field of view was 17.4 × 17.4 cm, and the pixel matrix was 512 × 512. A soft tissue reconstruction algorithm was applied.

ROI analysis—From the images obtained, a contrast concentration–versus-time curve was generated from operator-defined ROIs by use of custom software in an engineering software program.d The ROI tool was a shapeable ellipse that was drawn on an image within the series that included contrast medium within the vasculature. The software then applied the ROI, after correction for any motion identified with the fiducial markers, to every CT image. To determine BF to the laminae, separate ROIs were chosen on the dorsal, dorsomedial, and dorsolateral aspects of the laminae as well as on an artery in the image; the latter ROI was used to define the arterial input function (Figure 1). The arterial input ROI was drawn around a small artery just medial to the abaxial margin of the distal sesamoid bone. The laminar ROI was drawn in the shape of a narrow ellipse with margins that were closely associated with the areas of laminar BF, whereas the arterial ROI was drawn in the shape of a small circle to approximate the margins of an artery within the image. The locations of the ROIs were consistent and empirically chosen so that the dorsal ROI was located on dorsal midline and the dorsomedial and dorsolateral ROIs approximately 30 degrees medial and lateral from dorsal midline, respectively. The length of each ROI was approximately 1 cm. Blood flow (mL•min−1•mL−1) was calculated by use of measurements obtained from time-versus-contrast enhancement or density curves (Figure 2) for tissue and arterial input ROIs and by use of the Mullani-Gould formula as follows:

article image

Figure 1—
Figure 1—

Repetitive 10-mm collimated CT images of the laminae and third phalanx of a forelimb of a horse without laminitis acquired via DCE-CT prior to, during, and after infusion of ionic iodinated contrast medium into the median or medial palmar artery. All images are oriented so that the dorsal aspect of the limb is toward the top, the medial aspect is to the left, and the lateral aspect is to the right. A—Image obtained prior to infusion (time [t] = 0 seconds). B—Image obtained during infusion (t = 10 seconds). The white ellipses are representations of the ROI drawn around the dorsal, dorsomedial, and dorsolateral laminar regions. The white arrow denotes the ROI drawn around an artery located medial to the distal sesamoid (navicular) bone. C—Image obtained during infusion (t = 30 seconds). D—Image obtained during infusion (t = 40 seconds). E—Image obtained during infusion (t = 60 seconds). F—Image obtained after infusion (t = 90 seconds). The round white structure in the bottom right of each image is a fiducial marker (aluminum rod) affixed to the palmar and lateral aspect of the digit.

Citation: American Journal of Veterinary Research 69, 3; 10.2460/ajvr.69.3.371

Figure 2—
Figure 2—

Time-versus-density curve derived via DCE-CT for a regional artery (A) and the ROIs around the dorsal (crosses), dorsomedial (squares), and dorsolateral (triangles) laminar regions (B) in a forelimb of a horse without laminitis. Notice that the scales of the y-axes in panel A and B are different.

Citation: American Journal of Veterinary Research 69, 3; 10.2460/ajvr.69.3.371

This method of blood flow estimation has been validated previously against a fluorescent microsphere technique.26

Patlak analysis has been previously described26 to calculate tissue contrast medium clearance VPM (mL•min−1•mL−1) in tissue. Patlak analysis uses a 2-compartment model theory to determine the rate constant of tissue uptake of a tracer between the intravascular and extravascular spaces29 (Appendix). This technique was originally described for nuclear imaging techniques and has also been applied to DCE-CT.30–32 By mathematical manipulation of the time-density data in relation to an arterial input function, a linear equation is created in which the slope approximates VPM and the y-intercept estimates the fraction of the tissue composed of blood vessels (FVV). For the dorsal, dorsolateral, and dorsomedial laminae, the ROIs were drawn and calculations were performed on 2 occasions by 1 of the authors (EFK). Close inspection of the ROIs and the data produced indicated that ROI drawing was improved in the second set of data. More specifically, better care was taken to exclude avascular cornified tissue and limit ROI boundaries to vascularized laminae in the second set of data. For this reason, statistical analyses were performed on the second measurements only. Blood flow values were adjusted and normalized to the FVV obtained in the Patlak calculations. Fractional vascular volume is reported without units as it represents the proportion of the tissue within the ROI that is vascular.

Statistical analysis—All statistical analysis was performed by use of commercially available software.e A single-factor ANOVA was used to compare the mean values for BF, VPM, and FVV in the dorsal, dorsomedial, and dorsolateral regions of the laminae. A Student t test was used to identify significant differences among regions when ANOVA results indicated a disparity. Linear regression was performed to determine the relationship between FVV and BF. A value of P < 0.05 was considered significant. Blood flow values were adjusted and normalized by FVV to allow direct comparison of the individual vessel flow in the dorsal laminar region to that of the dorsolateral or dorsomedial laminar region.

Results

The technique was completed successfully in all horses. No complication related to catheter placement, contrast agent administration, or anesthesia was detected in any horse.

Values for BF, VPM, FVV, and normalized BF were obtained (Table 1). Blood flows in the dorsal, dorsomedial, and dorsolateral laminar regions were not significantly (P = 0.06) different. The ANOVA identified a significant (P = 0.03) difference in VPM between dorsal and dorsomedial laminar regions. The dorsal laminar VPM was significantly (P = 0.004) less than the dorsomedial laminar VPM. No significant difference in VPM between the dorsal and dorsolateral laminar regions (P = 0.06) or between the dorsomedial and dorsolateral laminar regions (P = 0.64) was detected.

Table 1—

Mean ± SD BF, VPM, FVV, and normalized blood fow (BF/FW) in dorsal, dorsomedial, and dorsolateral laminar regions of the forelimbs of 9 horses (1 limb/horse) assessed by use of DCE-CT.
Laminar locationBF (mL•min-1•mL-1)VPM (mL•min-1•mL-1)FWNormalized BF (mL•min-1•mL-1)
Dorsal0.43 ± 0.210.09 ± 0.03*0.63 ± 0.20†‡0.67 ± 0.18
Dorsomedial0.26 ± 0.160.16 ± 0.06*0.37 ± 0.14†0.67 ± 0.24
Dorsolateral0.24 ± 0.160.12 ± 0.060.34 ± 0.17‡0.69 ± 0.21

Dorsal laminar VPM was significantly (P < 0.05) lower than dorsomedial laminar VPM.

Dorsal laminar FW was significantly (P < 0.05) higher than the dorsomedial laminar FW.

Dorsal laminar FW was significantly (P < 0.05) higher than the dorsolateral laminar FW.

The ANOVA identified a significant (P = 0.02) difference between FVV among the 3 regions. In the dorsal aspect of the lamina, FVV was 0.67 ± 0.20. The dorsal laminar FVV was significantly higher than the dorsomedial laminar FVV (0.37 ± 0.14; P = 0.02) and dorsolateral laminar FVV (0.34 ± 0.17; P = 0.02). There was no significant (P = 0.91) difference in FVV between the dorsomedial and dorsolateral laminar regions.

Apparent relationships between FVV and BF in all areas of the hoof were identified (Figure 3). The normalized BF values for the dorsal, dorsomedial, and dorsolateral laminar locations were 0.67 ± 0.18 mL•min−1•mL−1, 0.67 ± 0.24 mL•min−1•mL−1, and 0.69 ± 0.21 mL•min−1•mL−1, respectively. These values did not differ significantly (P = 0.98).

Figure 3—
Figure 3—

Linear regression analysis of dorsal (A), dorsomedial (B), and dorsolateral (C) laminar BF versus FVV derived via DCE-CT from the forelimbs of 9 horses without laminitis (1 limb/horse). For dorsal laminar BF versus FVV, y = 0.9178x − 0.1025 (R2 = 0.9812); for dorsomedial laminar BF versus FVV, y = 1.0178x − 0.0989 (R2 = 0.8709); and for dorsolateral laminar BF versus FVV, y = 0.8778x − 0.0537 (R2 = 0.8614).

Citation: American Journal of Veterinary Research 69, 3; 10.2460/ajvr.69.3.371

Discussion

Dynamic contrast-enhanced CT was used in the present study to rapidly and noninvasively evaluate the hemodynamic variables of laminar BF and VPM in horses that did not have signs of laminitis. Results indicated that VPM was significantly lower in the dorsal laminar region, compared with the dorsomedial and dorsolateral laminar regions. However, the consistency of values calculated in our study suggests that interhorse variation of this measure is small. Similarly, the FVV was significantly higher in the dorsal laminar region than the value in either the dorsolateral or dorsomedial laminar region. Conversely, BF did not differ significantly among the 3 regions evaluated, which was likely attributable to the high SD of values. As one might expect, BF is strongly correlated with the vascular density in the ROI. Normalization of blood flow values on the basis of vascular density revealed that the flow in any given vessel was more consistent (evidenced by lower SD values). Furthermore, overall BF differences among the dorsal, dorsolateral, and dorsomedial laminar locations were more related to the number rather than the flow volume of local blood vessels. The implication of these findings in the development and progression of laminitis remains to be elucidated.

Dynamic contrast-enhanced CT has been established as a valid tool to yield quantitative information regarding several BF variables.24–27 Modern helical CT scanners can acquire data repetitively from the same physical location by scanning rapidly without table translation. With the administration of commercially available iodinated contrast medium, time-density data are acquired that yield quantitative measures similar to the information previously rendered by radiopharmaceutical tracers used in functional nuclear medicine studies. The advantage of DCE-CT over these scintigraphic methods is that the spatial resolution is far superior, thereby allowing more precise placement of ROIs.33 In the present study, ROI assignment became more precise with practice and when an effort was made to exclude the cornified, avascular tissue of the hoof wall.

The ability to derive quantitative BF and VPM information via DCE-CT is dependent on several key properties of an intravascular iodinated contrast medium. First, there is a linear relationship between iodine concentration in tissue and the relative density of tissue measured by the CT scanner (in HUs).25,34 Further, an iodinated contrast medium mixes rapidly in circulating plasma and quickly leaks out of the vascular space into the interstitium, whereas only a small percentage (1% to 2%) enters into intracellular spaces.35,36 On the basis of these general properties of iodinated contrast medium, BF can be measured in the early phase of contrast medium ingress into a given region and VPM can be estimated in the later phase.

Blood flow per unit volume of tissue was calculated in the present study by use of the Mullani-Gould relationship, a method of calculation that has been previously validated.26 This method makes important assumptions about BF.36 It assumes that contrast medium entering the region must pass in a linear fashion through successively smaller vessels and that the maximum contrast medium concentration in tissue precedes the beginning of tissue wash-out or elimination of contrast medium. The ideal arterial contrast medium concentration–versus-time input function has the shape of a delta function (square wave) with instantaneous arrival and departure.37 When contrast medium is administered through a peripheral vein, the shape of the arterial contrast concentration–versus-time curve develops a Gaussian (bell) shape as a result of passage through the cardiopulmonary circulation.37 In our study, a direct arterial injection was used, which resulted in an arterial time-density curve that more closely resembled a delta function with a very short time to maximum contrast medium concentration.

Vascular permeability is defined as the net flux of fluid from the intravascular space into the interstitial space. The Patlak method of calculation used in the present study is based on a 2-compartment model wherein contrast medium accumulation in the ROI is represented by contrast medium in the intravascular space and the interstitial space.27,36 During data collection, a timedensity curve is made for the ROI but also for an artery included within the image. The arterial time-density curve provides information regarding the intravascular contrast medium component, which should mirror the plot of vascular contrast medium concentration in the ROI. Vascular permeability is then calculated as the rate constant of contrast medium moving from the intravascular space into the interstitium.

To our knowledge, only 1 attempt at estimation of VPM alterations associated with laminitis in horses has been performed in vivo, and that investigation used lymphatic flow as an indirect measure.23 Given that there is histologic evidence to support ischemia-reperfusion as a contributor to laminar damage, it is reasonable to anticipate that both BF and VPM will be altered in this disease.9,38 Several reasons exist to predict that VPM in particular will be altered. It is known that small blood vessel pressure increases during the acute phase of laminitis.23 Because the vascular supply in the foot operates with high hydrostatic pressures,39,40 the capillaries of the foot are relatively permeable to macromolecules,41 and the venules of the lamina are apparently more reactive to vasoactive stimulation,42 increases in laminar blood vessel pressure would likely force fluid into the interstitium by increasing hydrostatic pressure. Furthermore, arteriovenous anastomoses exist in the dermal lamina and their regulation is not clearly understood; however, if venous hypertension exists, blood is thought to be shunted away from the tissues into venous circulation.43 The combination of high hydrostatic pressure with relatively leaky vascular endothelium suggests that the laminae could be prone to abnormalities in VPM. An increased amount of interstitial fluid in the confined physical space of the hoof capsule will potentially further increase interstitial hydrostatic pressure, preferentially affecting the venules, and thereby shunt or increase net fluid flux into the interstitial space. This shunting would be less than the resolving power of CT and could introduce bias. Shunting of contrast medium through these vessels would be interpreted as areas of perfused tissue while actually representing regions with poor cellular perfusion.

In horses, DCE-CT offers a means of BF and VPM evaluation; absolute vascular flow, VPM, and vascular volume values can be assessed, or changes in these variables over time can be monitored. In the present study, this novel, noninvasive technique proved to be repeatable; following normalization for vascular volume, consistent absolute values for BF to laminar regions in the forelimbs of horses were obtained. Vascular permeability values were similarly consistent. We anticipate that this technique will allow for a greater understanding of the pathophysiology of laminitis in horses if applied in research and clinical settings.

ABBREVIATIONS

BF

Blood flow

VPM

Vascular permeability

CT

Computed tomography

HU

Hounsfield unit

DCE-CT

Dynamic contrast-enhanced computed tomography

ROI

Region of interest

FVV

Fractional vascular volume
a.

MEDRAD Vistron CT, MEDRAD Inc, Indianola, Pa.

b.

HiSpeed FX/I, GE Medical Systems, Milwaukee, Wis.

c.

RenoCal-76 (400 mg of iodine/mL), Bracco Diagnostics, Princeton, NJ.

d.

Matlab 7.0, MathWorks Inc, Natick, Mass.

e.

Excel, version 11.3.6, Microsoft Corp, Redmond, Wash

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    Cenic A, Nabavi DG, Craen RA, et al. A CT method to measure hemodynamics in brain tumors: validation and application of cerebral blood flow maps. AJNR Am J Neuroradiol 2000;21:462–470.

    • Search Google Scholar
    • Export Citation
  • 28.↑

    Puchalski SM, Galuppo LD, Hornof WJ, et al. Intraarterial contrast-enhanced computed tomography of the equine distal extremity. Vet Radiol Ultrasound 2007;48:21–29.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.↑

    Dawson P. Functional imaging in CT. Eur J Radiol 2006;60:331–340.

  • 30.

    Dawson P, Peters AM. Functional imaging in computed tomography. The use of contrast-enhanced computed tomography for the study of renal function and physiology. Invest Radiol 1993;28(suppl 5):S79–S84.

    • Search Google Scholar
    • Export Citation
  • 31.

    Dawson P, Peters M. Dynamic contrast bolus computed tomography for the assessment of renal function. Invest Radiol 1993;28:1039–1042.

  • 32.

    Patlak CS, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 1983;3:1–7.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.↑

    Bushberg J, Seibert J, Leidholdt E Jr, et al. Introduction to medical imaging. In: The essential physics of medical imaging. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2002;15.

    • Search Google Scholar
    • Export Citation
  • 34.

    Hindmarsh T. Elimination of water-soluble contrast media from the subarachnoid space. Investigation with computerized tomography. Acta Radiol Suppl 1975;346:45–49.

    • Search Google Scholar
    • Export Citation
  • 35.

    Dawson P. Dynamic contrast-enhanced functional imaging with multi-slice CT. Acad Radiol 2002;9(suppl 2):S368–S370.

  • 36.↑

    Dawson P. Functional imaging in CT. Eur J Radiol 2006;60:331–340.

  • 37.↑

    Blomley M, Dawson P. Bolus dynamics: theoretical and experimental aspects. Br J Radiol 1997;70:351–359.

  • 38.

    Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc Surg 2002;10:620–630.

  • 39.

    Eaton SA, Allen D, Eades SC, et al. Digital Starling forces and hemodynamics during early laminitis induced by an aqueous extract of black walnut (Juglans nigra) in horses. Am J Vet Res 1995;56:1338–1344.

    • Search Google Scholar
    • Export Citation
  • 40.

    Allen D Jr, Clark ES, Moore JN, et al. Evaluation of equine digital Starling forces and hemodynamics during early laminitis. Am J Vet Res 1990;51:1930–1934.

    • Search Google Scholar
    • Export Citation
  • 41.↑

    Allen D Jr, Korthius RJ, Clark ES. Capillary permeability to endogenous macromolecules in the equine digit. Am J Vet Res 1988;49:1609–1612.

    • Search Google Scholar
    • Export Citation
  • 42.↑

    Peroni JF, Moore JN, Noschka E, et al. Predisposition for venoconstriction in the equine laminar dermis: implications in equine laminitis. J Appl Physiol 2006;100:759–763.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43.↑

    Molyneux GS, Haller CJ, Mogg K, et al. The structure, innervation and location of arteriovenous anastomoses in the equine foot. Equine Vet J 1994;26:305–312.

    • Crossref
    • Search Google Scholar
    • Export Citation

Appendix

Theory of Patlak analysis as applied to DCE-CT data for the determination of laminar blood flow variables in the distal portion of the forelimb of horses without laminitis.
app

Contributor Notes

Supported by the Center for Equine Health, UC Davis, which is supported by the Oak Tree Racing Association, The State of California Pari-Mutuel Fund, and contributions by private donors.

Presented at the 2005 American College of Veterinary Internal Medicine Forum, Baltimore, June 2005.

The authors thank Richard F. Larson for technical assistance in imaging and equipment operation and Tanya Garcia-Nolen for computer programming and program operation.

Address correspondence to Dr. Puchalski.
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Mar 2008
  • Figure 1—
    View in gallery
    Figure 1—

    Repetitive 10-mm collimated CT images of the laminae and third phalanx of a forelimb of a horse without laminitis acquired via DCE-CT prior to, during, and after infusion of ionic iodinated contrast medium into the median or medial palmar artery. All images are oriented so that the dorsal aspect of the limb is toward the top, the medial aspect is to the left, and the lateral aspect is to the right. A—Image obtained prior to infusion (time [t] = 0 seconds). B—Image obtained during infusion (t = 10 seconds). The white ellipses are representations of the ROI drawn around the dorsal, dorsomedial, and dorsolateral laminar regions. The white arrow denotes the ROI drawn around an artery located medial to the distal sesamoid (navicular) bone. C—Image obtained during infusion (t = 30 seconds). D—Image obtained during infusion (t = 40 seconds). E—Image obtained during infusion (t = 60 seconds). F—Image obtained after infusion (t = 90 seconds). The round white structure in the bottom right of each image is a fiducial marker (aluminum rod) affixed to the palmar and lateral aspect of the digit.

  • Figure 2—
    View in gallery
    Figure 2—

    Time-versus-density curve derived via DCE-CT for a regional artery (A) and the ROIs around the dorsal (crosses), dorsomedial (squares), and dorsolateral (triangles) laminar regions (B) in a forelimb of a horse without laminitis. Notice that the scales of the y-axes in panel A and B are different.

  • Figure 3—
    View in gallery
    Figure 3—

    Linear regression analysis of dorsal (A), dorsomedial (B), and dorsolateral (C) laminar BF versus FVV derived via DCE-CT from the forelimbs of 9 horses without laminitis (1 limb/horse). For dorsal laminar BF versus FVV, y = 0.9178x − 0.1025 (R2 = 0.9812); for dorsomedial laminar BF versus FVV, y = 1.0178x − 0.0989 (R2 = 0.8709); and for dorsolateral laminar BF versus FVV, y = 0.8778x − 0.0537 (R2 = 0.8614).

Figure 1—

Repetitive 10-mm collimated CT images of the laminae and third phalanx of a forelimb of a horse without laminitis acquired via DCE-CT prior to, during, and after infusion of ionic iodinated contrast medium into the median or medial palmar artery. All images are oriented so that the dorsal aspect of the limb is toward the top, the medial aspect is to the left, and the lateral aspect is to the right. A—Image obtained prior to infusion (time [t] = 0 seconds). B—Image obtained during infusion (t = 10 seconds). The white ellipses are representations of the ROI drawn around the dorsal, dorsomedial, and dorsolateral laminar regions. The white arrow denotes the ROI drawn around an artery located medial to the distal sesamoid (navicular) bone. C—Image obtained during infusion (t = 30 seconds). D—Image obtained during infusion (t = 40 seconds). E—Image obtained during infusion (t = 60 seconds). F—Image obtained after infusion (t = 90 seconds). The round white structure in the bottom right of each image is a fiducial marker (aluminum rod) affixed to the palmar and lateral aspect of the digit.
Figure 2—

Time-versus-density curve derived via DCE-CT for a regional artery (A) and the ROIs around the dorsal (crosses), dorsomedial (squares), and dorsolateral (triangles) laminar regions (B) in a forelimb of a horse without laminitis. Notice that the scales of the y-axes in panel A and B are different.
Figure 3—

Linear regression analysis of dorsal (A), dorsomedial (B), and dorsolateral (C) laminar BF versus FVV derived via DCE-CT from the forelimbs of 9 horses without laminitis (1 limb/horse). For dorsal laminar BF versus FVV, y = 0.9178x − 0.1025 (R2 = 0.9812); for dorsomedial laminar BF versus FVV, y = 1.0178x − 0.0989 (R2 = 0.8709); and for dorsolateral laminar BF versus FVV, y = 0.8778x − 0.0537 (R2 = 0.8614).
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    Cenic A, Nabavi DG, Craen RA, et al. A CT method to measure hemodynamics in brain tumors: validation and application of cerebral blood flow maps. AJNR Am J Neuroradiol 2000;21:462–470.

    • Search Google Scholar
    • Export Citation
  • 28.

    Puchalski SM, Galuppo LD, Hornof WJ, et al. Intraarterial contrast-enhanced computed tomography of the equine distal extremity. Vet Radiol Ultrasound 2007;48:21–29.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Dawson P. Functional imaging in CT. Eur J Radiol 2006;60:331–340.

  • 30.

    Dawson P, Peters AM. Functional imaging in computed tomography. The use of contrast-enhanced computed tomography for the study of renal function and physiology. Invest Radiol 1993;28(suppl 5):S79–S84.

    • Search Google Scholar
    • Export Citation
  • 31.

    Dawson P, Peters M. Dynamic contrast bolus computed tomography for the assessment of renal function. Invest Radiol 1993;28:1039–1042.

  • 32.

    Patlak CS, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 1983;3:1–7.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Bushberg J, Seibert J, Leidholdt E Jr, et al. Introduction to medical imaging. In: The essential physics of medical imaging. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2002;15.

    • Search Google Scholar
    • Export Citation
  • 34.

    Hindmarsh T. Elimination of water-soluble contrast media from the subarachnoid space. Investigation with computerized tomography. Acta Radiol Suppl 1975;346:45–49.

    • Search Google Scholar
    • Export Citation
  • 35.

    Dawson P. Dynamic contrast-enhanced functional imaging with multi-slice CT. Acad Radiol 2002;9(suppl 2):S368–S370.

  • 36.

    Dawson P. Functional imaging in CT. Eur J Radiol 2006;60:331–340.

  • 37.

    Blomley M, Dawson P. Bolus dynamics: theoretical and experimental aspects. Br J Radiol 1997;70:351–359.

  • 38.

    Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc Surg 2002;10:620–630.

  • 39.

    Eaton SA, Allen D, Eades SC, et al. Digital Starling forces and hemodynamics during early laminitis induced by an aqueous extract of black walnut (Juglans nigra) in horses. Am J Vet Res 1995;56:1338–1344.

    • Search Google Scholar
    • Export Citation
  • 40.

    Allen D Jr, Clark ES, Moore JN, et al. Evaluation of equine digital Starling forces and hemodynamics during early laminitis. Am J Vet Res 1990;51:1930–1934.

    • Search Google Scholar
    • Export Citation
  • 41.

    Allen D Jr, Korthius RJ, Clark ES. Capillary permeability to endogenous macromolecules in the equine digit. Am J Vet Res 1988;49:1609–1612.

    • Search Google Scholar
    • Export Citation
  • 42.

    Peroni JF, Moore JN, Noschka E, et al. Predisposition for venoconstriction in the equine laminar dermis: implications in equine laminitis. J Appl Physiol 2006;100:759–763.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43.

    Molyneux GS, Haller CJ, Mogg K, et al. The structure, innervation and location of arteriovenous anastomoses in the equine foot. Equine Vet J 1994;26:305–312.

    • Crossref
    • Search Google Scholar
    • Export Citation

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