MAGNETIC RESONANCE IMAGING OF THE INITIAL ACTIVE STAGE OF EQUINE LAMINITIS AT 4.7 T

MAGNETIC RESONANCE IMAGING OF THE INITIAL ACTIVE STAGE

OF EQUINE LAMINITIS AT 4.7T

JASON B. ARBLE, JOHN S. MATTOON, WM. TOD DROST, STEVEN E. WEISBRODE, PETER A. WASSENAAR,XUELIANG PAN, ROBERT J. HUNT, JAMES K. BELKNAP

Equine laminitis is a severely debilitating disease. There is a poor understanding of the underlying pathophys-

iology, and traditional imaging modalities have limited diagnostic capacity. High field strength magnetic

resonance (MR) imaging allows direct visualization of the laminae, which other modalities do not. This would

prove useful both in assessment of clinical patients and in further investigation into the pathophysiology of the

disease. The objective of this study was to characterize the anatomic changes within the equine foot associated

with the initial active stage of laminitis. Images obtained using a 4.7T magnet were compared with digital

radiographs using histologic diagnosis as the reference standard. Objective measurements and subjective eval-

uation for both modalities were evaluated for the ability to predict the histologic diagnosis in horses with clinical

signs of laminitis as well as in clinically normal horses and horses that were in a population at risk for developing

laminitis. Signal intensity and architectural changes within the corium and laminae were readily seen at 4.7T,

and there was a strong association with the histologic diagnosis of active laminitis. Measurements obtained with

MR imaging were more sensitive and specific predictors of laminitis than those obtained radiographically.

Subjective evaluation with MR imaging was more sensitive than with radiography and should become more

specific with greater understanding of normal anatomy. Veterinary Radiology & Ultrasound, Vol. 50, No. 1,

2009, pp 3–12.

Key words: equine, laminitis, MRI.

Introduction

LAMINITIS, CHARACTERIZED BY loss of the support of the

distal phalanx due to separation of the dermal and

epidermal laminae, can occur secondary to equine systemic

inflammatory disease, dietary change, or carbohydrate

overload. The exact pathophysiologic basis of laminitis

is unclear.1–3 An imaging modality that allowed direct

visualization of the laminae might enhance the under-

standing of laminitis.

The appearance of chronic laminitis has been described

using magnetic resonance (MR) imaging,4,5 but the changes

seen with MR imaging during the initial phase are unchar-

acterized. It was our purpose to identify the specific changes

seen in horses during the initial active phase of laminitis

using MR imaging and compare the imaging findings with

histologic appearance of the laminae. Further, we compared

radiographic and MR imaging findings using the histologic

appearance as the reference standard. We also assessed

whether the changes seen in horses with initial active

laminitis may be seen in horses that are at risk for devel-

oping acute laminitis but do not yet exhibit clinical signs.

Materials and Methods

Adult, full-sized horses with acute active laminitis, or

current disease known to predispose to acute laminitis,

having undergone euthanasia were considered for inclusion

in this study. All horses were euthanized due to normal

clinical course without regard to this study. Horses with

a prior history of laminitis in the affected limbs were

excluded. The initial active phase of laminitis was defined

as foot pain with increased temperature of the dorsal hoof

surface, with or without bounding digital pulses, for a

duration of less than 15 days.

Twenty-eight horses ranging in age from 2 to 23 years

met the criteria for inclusion in the study. If laminitis was

detected clinically in the front limbs, then both front limbs

and one hind limb were collected. If laminitis was detected

Funded by the American College of Veterinary Radiology and TheOhio State University Intramural Equine Research Fund.

Presented at the International Society for Magnetic Resonance in Med-icine, Berlin, Germany, May 2007, and in part at the Joint ACVR/IVRAMeeting, Vancouver, Canada, August 2006.

Address correspondence and reprint requests to Jason B. Arble, at theabove address. E-mail: [email protected]

Dr. Arble’s present address is Center for Veterinary Health Sciences,Oklahoma State University, Stillwater, OK.

Dr. Mattoon’s present address is Department of Veterinary ClinicalSciences, Washington State University, Pullman, WA.

Received November 5, 2007; accepted for publication December 6,2008.

doi: 10.1111/j.1740-8261.2008.01483.x

From the Department of Veterinary Clinical Sciences (Arble, Mattoon,Drost, Belknap), Department of Veterinary Biosciences, College of Vet-erinary Medicine (Weisbrode), Department of Radiology, College ofMedicine (Wassenaar), Department of Statistics (Pan), The Ohio StateUniversity, Columbus, OH 43210, and Hagyard-Davidson-McGee, Lex-ington, KY (Hunt).

3

only in the hind limbs, then both hind limbs and one front

limb were collected. All four extremities were collected if

the horse had laminitis in both the front and rear limbs.

This resulted in 81 feet being studied.

Horses were divided into three groups based on clinical

presentation and possible risk for developing acute lamini-

tis. Group 1 consisted of nine horses that were suffering

from an initial active onset of laminitis for less than 14 days

at the time of euthanasia. Group 2 consisted of 10 horses

that were suffering from diseases known to predispose

to acute laminitis but did not have clinical signs of acute

laminitis at the time of euthanasia. Diseases in Group 2

horses consisted of gastrointestinal disease in nine and cat-

astrophic skeletal injury in one. The nine horses in Group 3

were used as normal controls. These horses had no prior

history of laminitis and were euthanized for causes that are

not associated with a predisposition to acute laminitis.

After euthanasia, the shoes were removed if present and

the distal extremity was disarticulated from the limb at the

metacarpo(tarso)phalangeal joint. The feet were cleaned

and all inorganic and metallic material removed. Speci-

mens were stored in a walk-in cooler until imaging could

be performed. Specimens that could not be imaged within

4 days were frozen at �201C. Frozen specimens were

allowed to thaw 18–24 h before imaging.

Radiographs of each foot were made with an indirect flat

panel digital radiography system.� Lateral-to-medial and

dorsal 601 proximal–palmarodistal/plantarodistal projec-

tions were made for each foot and stored on a server

maintained onsite and dedicated to storage of digital im-

ages. Images were stored in DICOM format and evaluated

using an eFilmw imaging workstation. Any metallic debris

detected radiographically was removed before MR imaging.

All distal extremities were imaged on a 4.7T/40 cm

magnet controlled by a Bruker Avancez console. After a

localizer spin echo sequence, T2�-weighted images were

acquired in transverse and sagittal planes using a 3D gra-

dient echo (GRE) sequence. T1 and proton density (PD)-

weighted images were acquired in the transverse plane. The

sequence parameters are summarized in Table 1.

All feet were sectioned within 2 hours of completion of

imaging. Using a band saw, sagittal and transverse cuts

were made through the dorsal hoof wall and distal phalanx

and sections from the mid-portion of the dorsal hoof wall

in both planes were harvested. Tissues specimens were fixed

in formalin for a minimum of 48 h before being trimmed

for paraffin embedding and tissue sectioning. Each slide

contained both a sagittal and transverse section that in-

cluded as much of the corium and keratinized hoof wall as

possible and was stained with hemotoxylin and eosin. All

slides were evaluated by a board-certified veterinary

pathologist (S.E.W.) experienced in equine disease; the

pathologist was not aware of the history or imaging find-

ings. Histologic diagnosis of normal or laminitis was made

based on laminar disorganization and necrosis, pyknosis,

and rhexis of the epidermal laminae.6 All samples were

evaluated for separation between the dermal and epidermal

laminae and evidence of freezing-induced artifacts and

tissue necrosis.

All radiographic and MR images were randomized sep-

arately and reviewed by two board-certified veterinary ra-

diologists (J.S.M. and W.T.D.) and one board-certified

equine surgeon (J.K.B.). All reviewers were unaware of

the clinical status and histologic findings. Measurements

included proximal and distal dorsal hoof wall thickness and

the dorsal hoof wall-to-distal phalanx ratio.7 Representative

transverse T2� 3D GRE images from the proximal, middle,

and distal one-third of each foot were identified by dividing

the soft tissues dorsal to the distal phalanx into equal thirds

and then selecting a slice from the center of each region

(Fig. 1). Each image was evaluated for alteration of the

following: corium architecture, corium signal intensity,

laminar architecture, laminar signal intensity, and laminar

separation. Each change was graded normal, mild, moder-

ate, or severe: grades 1–4, respectively. Quantitative

measurements of the MR images included: thickness of

the corium, laminae, dermal tissue (laminae plus corium),

and the ratio of laminae to total dermal tissue (Fig. 2). The

laminae-to-dermis ratio was calculated by dividing the

thickness of the laminae by the total thickness of the dermal

tissue at the same location. All radiographic and MR image

measurements were made by a single individual (J.B.A.).

Changes noted by one author (J.B.A.) on a pilot study

were used as categories to be evaluated by each observer

when reviewing the representative MR images from each

foot. Pearson correlation was used to evaluate the associ-

ation between a change noted with MR imaging and a

histologic diagnosis of laminitis. Each category was also

assigned a numeric qualifier from 1 (normal) to 4 (severe

change). A chi-squared analysis was performed for each

category at each level (proximal, middle, distal) to detect

any significant difference for the number values assigned

for each category between normal and laminitic feet. The

Table 1. Magnetic Resonance Imaging Sequence Parameters

FOV(cm3/cm2) Matrix

TR(ms)

TE(ms)

Thickness/Gap (mm)

T2�-weighted3DGRE

12 � 12 � 8 384 � 384 � 40 16.5 3.7 1.3 � 1.3

T1 weighted 12 � 12 256 � 256 700 4.3 2.5 � 2.5PD weighted 12 � 12 256 � 256 3000 4.3 2.5 � 2.5

FOV, field of view; TR, time to repetition; TE, time to echo; 3DGRE,

three-dimensional gradient recall echo; PD, proton density.

�Eklin Medical Systems, Santa Clara, CA.wMerge Healthcare, Milwaukee, WI.zBruker, Ettlingen, Germany.

4 ARBLE ET AL. 2009

probability of a change being detected was also calculated

with respect to the histologic diagnosis.

A two-sample Student’s t-test was used to compare the

mean differences in measurements obtained radiographi-

cally vs. MR imaging, in normal vs. laminitic feet. Dot

plots were constructed to compare the distribution of mea-

surement values and to determine cut points for the lami-

nae-to-dermis ratio in MR images and dorsal hoof wall-

to-distal phalanx ratio in radiographs. The sensitivity,

specificity, positive predictive value, and negative predictive

value for the three different foot levels were calculated us-

ing the derived cut point.

The ability to specifically identify laminar separation us-

ing MR imaging and radiography was evaluated in terms of

sensitivity and specificity using histologically evident sepa-

ration as the standard. The ability to predict a histologic

diagnosis of laminitis based on the observed changes was

evaluated by calculating the sensitivity and specificity for

the detection of an abnormality in each separate category.

Sensitivity and specificity for each abnormality were calcu-

lated with two different cut-off points. A cut point of 1

denoted that any abnormality from mild to severe (2–4) was

a prediction of disease. A cut point of 2 denoted that mild

changes (2) were considered normal while moderate to se-

vere changes (3 or 4) were predictors of laminitis. Sensitivity

and specificity were also calculated for each observer for the

ability to correctly come to the diagnosis of laminitis or

normal for both MR imaging and radiography.

Results

Data from one foot in Group 2 was corrupted beyond

retrieval. A single foot from a horse suffering from a

nonweight-bearing injury in the contralateral limb was in-

cluded, as the weight-bearing foot was at risk for support-

limb laminitis.

Nineteen of 27 feet in Group 1 horses, and two of 27 feet

in Group 2 horses were laminitic. All remaining feet were

normal.

The 3D GRE sequence transverse images (Fig. 3) were

characterized by the best anatomic detail and contrast

Fig. 3. T2�-weighted transverse image of a normal equine digit.

Fig. 2. Transverse T2�-weighted image illustrating the measurementsmade of the laminae and corium used to derive the laminae-to-dermis ratio.

Fig. 1. Sagittal T2�-weighted image of the equine digit. The transverselines represent the locations of the three transverse images provided to theobservers for evaluation of each foot.

5MRI OF INITIAL ACTIVE EQUINE LAMINITIS USING 4.7 TVol. 50, No. 1

resolution of the three MR imaging sequences performed

and was therefore exclusively used in the MR evaluations.

The normal corium and laminae had greater signal inten-

sity than the hoof wall and the cortical bone of the distal

phalanx. The internal portion of the hoof wall and the

medullary cavity of the distal phalanx had similar inter-

mediate signal intensity. The peripheral borders of the hoof

wall were not detectable due to a lack of signal from this

structure. The individual primary laminae were easily iden-

tified. Although differentiation between sensitive and

insensitive primary laminae was not possible in the MR

images, the epidermal laminae typically had a less intense

signal which was similar to the interior hoof wall, while the

dermal laminae were more hyperintense. The architecture

of the corium was readily identifiable with a heterogeneous

pattern that was interspersed with hyper- and hypointense

blood vessels. The margin between the corium and the

cortex of the distal phalanx was distinct and had an

undulating pattern. When compared with histologic

samples at 4 � magnification (Fig. 4), all of the anatomic

architecture was identifiable except the secondary laminae.

Ability to see the secondary laminae and consistently

differentiate the sensitive from insensitive primary laminae

was a limitation in MR anatomic resolution.

Examining the MR images, five specific changes were

identified that were likely associated with the initial active

stage of laminitis. Pearson correlation confirmed the asso-

ciation of histologically evident laminitis with all five

changes which included loss of normal corium architecture,

loss of laminar architecture, increased signal intensity in

the corium, increased signal intensity in the laminae, and

separation within the laminae (Table 2). When compared

with a transverse T2�-weighted MR image from a histo-

logically normal foot (Fig. 5), the above changes were

readily identified (Fig. 6).

There was marked alteration in the appearance of the

corium characterized by the lack of normal vasculature and

a homogeneous appearance with overall increased signal

intensity. The laminar layer was altered with multiple foci

of detail loss and, less commonly, a focal increase in signal

intensity. Disruption and distinct separation within the

laminae were readily seen beyond merely loss of normal

architectural distinction (Fig. 7).

There was a significant difference (Po0.001) in the

means of the laminae-to-dermis ratios between histologi-

cally normal vs. laminitic feet for proximal, middle, and

Fig. 6. Magnified transverse T2� image of the dorsal foot with initialactive laminitis. Note the change in corium intensity and homogeneity com-pared with Fig. 5. There is disruption and loss of uniformity in the laminae.A line of separation is identified by the arrowheads. HW, hoof wall; L,lamina; C, corium; P3, distal phalanx.

Fig. 5. Magnified transverse T2� image of a normal dorsal foot. Notethe heterogeneous appearance of the corium and uniform appearance ofthe laminae. HW, hoof wall; L, lamina; C, corium; P3, distal phalanx.

Table 2. Pearson Correlation of Magnetic Resonance Changes andHistological Diagnosis of Laminitis

CorrelationsLaminar

ArchitectureLaminarIntensity

CoriumArchitecture

CoriumIntensity Separation

Laminar intensity 0.762Coriumarchitecture

0.793 0.672

Corium intensity 0.738 0.643 0.888Separation 0.804 0.749 0.759 0.724Histological Dx 0.743 0.559 0.727 0.685 0.653

Fig. 4. Histological section of the interdigitation of normal laminae.H and E stain at 4� magnification.

6 ARBLE ET AL. 2009

distal locations, with the largest difference distally (Table

3). There was also a significant difference (Po0.001) be-

tween histologically normal and laminitic feet when com-

paring the maximum laminae-to-dermis ratio (Table 3).

Multiple cut points could be selected which influenced the

sensitivity and specificity when using the laminae-to-dermis

ratio to predict whether or not a foot will be histologically

normal or laminitic (Table 4).

Mean proximal hoof wall thickness, distal hoof wall

thickness, and dorsal hoof wall-to-distal phalanx ratio were

significantly different (Po0.001) between histologically

normal and laminitic feet (Tables 5 and 6).

The categorical observations (1, normal; 2, mild; 3,

moderate; 4, severe) for each abnormality detectable on

MR images were evaluated for the ability to predict

whether or not the foot was histologically laminitic or

normal and whether the location within the foot (proximal,

middle, distal) had any influence on the observers’ inter-

pretation (Figs. 8–12). The difference in the assigned grades

(normal, mild, moderate, severe) was statistically signifi-

cant (Po0.001) between normal and laminitic feet for all

categories even when the results for all three

observers were summed. Sensitivity and specificity for each

abnormality were calculated for the two different cut-off

points of 1 (any abnormality) or 2 (only moderate and

severe changes) and also with regard to the region of the

foot (Tables 7–11). For each abnormality, sensitivity was

better in the distal part of the foot, while specificity was

better in the proximal portion of the foot.

Fig. 7. T2� transverse MR image (A), lateromedial radiograph (B), andhistologic section with H and E stain (C) of a foot with laminitis. TheMR image(A) displays the alterations in the corium and lamina. An area of separation ismarked with an asterisk (�). An area of increased signal intensity is shown bythe white arrow. A focal hypointense signal is also present within the lamina(white arrowhead), likely representing gas or an area of acute focal hemorrhage.The mild degree of separation explains the lack of radiographic findings in thefoot (B). The histologic sample shows the separation between the epidermallamina and the dermal lamina. Note the area of hemorrhage exhibited by ac-cumulation of red blood cells (black arrow). HW, hoof wall; L, lamina; C,corium; P3, distal phalanx; EL, epidermal lamina; DL, dermal lamina.

Fig. 8. Distribution of total observed MR loss of laminar architecture withrespect to location and histological diagnosis. 1–4 on the x-axis denote theobservation of 1 (normal) to 4 (severe change) in the laminar architecture forthe proximal, middle, and distal images of each foot. The y-axis represents thenumber of feet that were assigned that grade by the observers (results aresummed for all three observers). ‘‘Norm’’ denotes a histologically normal footand ‘‘Lam’’ signifies that the observed foot was histologically laminitic.


Comparing MR and radiographic images, there was a

distinct difference in the sensitivity and specificity when

using objective measurements. Both were statistically sig-

nificant when comparing the means of normal vs. laminitic

feet for each test, but there was a large overlap of radio-

graphic measurements between normal and abnormal feet.

This was clearly demonstrated when comparing dot plots

derived from the radiographic measurements with dot plots

of the laminae-to-dermis ratio calculated from the MR

images (data not shown).

Comparing the subjective ability to make a diagnosis of

a laminitis vs. normal using radiography, the results for all

three observers were similar. The sensitivity for detecting

active laminitis was low (47.6–57.2%). The specificity,

however, was high (80.0–91.7%). The sensitivity for cor-

rectly identifying histologically laminitic feet with MR

imaging was much higher (95.2–100%), but the specificity

was more variable between observers (46.7–93.3%). This

indicates a large number of false-negative predictions of

laminitis using radiography, while there was a tendency for

a larger number of false-positive results with MR imaging.

Discussion

Based on our results, there are definitive changes that

occur with the initial active stage of laminitis and are

readily detected with MR imaging and these changes can-

not be detected with radiography. Fine anatomic detail is

readily achievable using high field strength magnets, which

makes direct evaluation of the laminae and corium possi-

ble.4,8 After subjective assessment of all sequences, it was

felt that the T2�-weighted 3D GRE sequence gave the best

anatomic detail coupled with the best contrast resolution in

both normal and laminitic feet. Distortion artifacts caused

by local field inhomogeneities as a result of residual metal

in the hoof did not impact the area of interest and were

only evident within millimeters of the shavings. The ability

to detect disruption within the primary laminae is very

important for evaluation of the laminitic horse and makes

MR imaging more sensitive in the initial phase of the dis-

ease when compared with radiography. The small foci of

increased signal intensity which may indicate focal edema

or necrosis were only visible with MR imaging. Addition-

Fig. 9. Distribution of total observed MR loss of corium architecture withrespect to location and histological diagnosis. 1–4 on the x-axis denote theobservation of 1 (normal) to 4 (severe change) in the corium architecture forthe proximal, middle, and distal images of each foot. The y-axis represents thenumber of feet that were assigned that grade by the observers (results aresummed for all three observers). ‘‘Norm’’ denotes a histologically normal footand ‘‘Lam’’ signifies that the observed foot was histologically laminitic.

Table 3. Student’s t-Test Results Comparing Means of Normal vs.Laminitic Feet Using MR-Derived Maximum Laminae-to-Dermis Ratio

for Proximal, Middle, and Distal Portions of the Foot and OverallMaximum

Mean (mm) SD (mm) T-value P-value

Maximum ratio of footNormal 0.64 0.05 �7.69 0.001Laminitic 0.83 0.11

Maximum ratio proximalNormal 0.6 0.05 �8.59 0.001Laminitic 0.78 0.1

Maximum ratio middleNormal 0.61 0.05 �8.12 0.001Laminitic 0.8 0.1

Maximum ratio distalNormal 0.62 0.06 �8.51 0.001Laminitic 0.82 0.1

Table 4. Sensitivity, Specificity, Positive Predictive Value (PPV), andNegative Predictive Value (NPV) for Maximum Laminae-to-Dermis Ra-tio for Proximal, Middle, and Distal Portions of the Foot and Overall

Maximum

Cut-OffValue

Sensitivity(%)

Specificity(%)

PPV(%)

NPV(%)

Maximum ratio of foot 0.7 81 93.3 81.0 93.30.75 81 98 94.4 93.70.81 81 100 100 93.8

Maximum ratio proximal 0.7 81 98 94.4 93.7Maximum ratio middle 0.7 81 98 94.4 93.7Maximum ratio distal 0.7 81 95 85.0 93.4

0.75 81 98 94.4 93.7

Table 5. Student’s t-Test Results Comparing Means of Normal vs.Laminitic Feet Using Dorsal Hoof Wall-to-Distal Phalanx Ratio,Proximal Hoof Wall Thickness, and Distal Hoof Wall Thickness

Measured Radiographically

Mean (mm) SD (mm) T-value P-value

Dorsal hoof wall-to-distal phalanx ratioNormal 26.99 2.13 �4.2 0.001Laminitic 30.56 3.69

Proximal dorsal hoof wall thickness (mm)Normal 18.38 1.54 �3.24 0.004Laminitic 20.76 3.24

Distal dorsal hoof wall thickness (mm)Normal 17.98 1.52 �3.95 0.001Laminitic 20.9 3.27

8 ARBLE ET AL. 2009

ally, the high detail allowed evaluation of adjacent struc-

tures such as the corium, which is often overlooked when

collecting specimens for histologic evaluation. The decrease

in vascular conspicuity and altered signal distribution

within the corium is a reminder that the laminar separation

may be an end product and not the only pathophysiologic

process responsible for the pain and inflammation during

the initial phase of the disease. The images obtained using

a high field strength magnet allowed more extensive

evaluation of the tissues adjacent to and associated with

the laminae.

Many studies have focused on the microenvironment of

the laminae and on the blood flow of the foot during acute

laminitis.9–22 However, seeing these changes in the corium

leads us to question the pathophysiologic processes occur-

ring in the tissue supporting and sustaining the laminae.

Further investigation into the hemodynamics and possible

inflammatory changes specifically within the dermal layer

would provide much needed insight into the mechanisms

that result in laminar necrosis and separation. Changes in

this location may also explain the hemodynamic alterations

in the larger vessels feeding the foot. MR imaging provides

a method for evaluation of this tissue that is difficult to

harvest and often overlooked.

The increased ability to detect changes in MR images

before radiographic evidence of physical breakdown of the

laminae not only allows avenues for further investigation

but also increases the ability of clinical evaluation. The

use of laminar separation as criteria for diagnosing acute

laminitis had a lower sensitivity and specificity than other

categories but may be a better prognostic indicator

regarding the outcome of the disease. Horses that had

histologic evidence of laminitis but were labeled normal in

regard to laminar separation onMR images are likely early

in the disease process.

Another potentially useful criterion in the evaluation of

the laminitic horse is the use of the laminae-to-dermis ratio.

This may have more clinical utility in lower field strength

Table 6. Sensitivity, Specificity, Positive Predictive Value (PPV), andNegative Predictive Value (NPV) for Radiographic Dorsal Hoof Wall-to-

Distal Phalanx Ratio

Cut-OffValue Sensitivity Specificity

PPV(%)

NPV(%)

Dorsal hoofwall-to-P3 ratio

0.3 11/21¼ 52.4% 55/60¼ 91.7% 42.30 84.60

Fig. 10. Distribution of total observedMR-altered laminar signal intensitywith respect to location and histological diagnosis. 1–4 on the x-axis denotethe observation of 1 (normal) to 4 (severe change) in laminar signal intensityfor the proximal, middle, and distal images of each foot. The y-axis representsthe number of feet that were assigned that grade by the observers (results aresummed for all three observers). ‘‘Norm’’ denotes a histologically normal footand ‘‘Lam’’ signifies that the observed foot was histologically laminitic.

Fig. 11. Distribution of total observed MR-altered corium signal intensitywith respect to location and histological diagnosis. 1–4 on the x-axis denote theobservation of 1 (normal) to 4 (severe change) in the corium signal intensity forthe proximal, middle, and distal images of each foot. The y-axis represents thenumber of feet that were assigned that grade by the observers (results aresummed for all three observers). ‘‘Norm’’ denotes a histologically normal footand ‘‘Lam’’ signifies that the observed foot was histologically laminitic.

Fig. 12. Distribution of total observed MR separation with respect tolocation and histological diagnosis. 1–4 on the x-axis denote the observationof 1 (normal) to 4 (severe change) of separation for the proximal, middle,and distal images of each foot. The y-axis represents the number of feet thatwere assigned that grade by the observers (results are summed for all threeobservers). ‘‘Norm’’ denotes a histologically normal foot and ‘‘Lam’’ sig-nifies that the observed foot was histologically laminitic.


magnets where individual laminae may not be seen but a

distinction between the corium and laminae is still possible.

Based on our results, a laminae-to-dermis ratio greater

than 0.7 is a good indicator of laminitis. It has been shown

that the laminae lengthen and attenuate in laminitis.4,5,16 It

may be inferred that an increased laminae-to-dermis ratio

is likely due to mechanical breakdown at the level of the

secondary laminae. Additionally, by using a ratio to eval-

uate the relative increase in laminae thickness, the cut point

is likely to be influenced less than an arbitrary measure-

ment if the angle of the image slice is not perpendicular to

the dorsal hoof wall.

We noticed a trend of abnormalities being more evident

in the distal region of the foot vs. the middle or proximal

regions. The increase in maximum laminae-to-dermis ratio

in the toe region of laminitic feet gave a greater disparity

between histologically normal vs. laminitic feet, allowing

greater sensitivity and specificity. These objective data sup-

port the toe region being most affected in chronic laminits.4

This is most evident with the loss of corium architecture

and increase in corium signal intensity. This is consistent

with the mechanical stresses being greatest in the toe region.

All subjective changes identified were highly correlated

with a histologic diagnosis of laminitis. Additionally,

despite the variation introduced by using three observers,

the grading of each category was significantly different

between histologically normal and laminitic feet. Further

investigation is necessary to evaluate the specific associa-

tion of MR changes to the specific histologic change. This

process is hampered by the necessity to section the exact

tissue in question on the MR image. One limitation of our

study was that a single sample from the middle of the foot

was obtained for histologic diagnosis. Another fact to

consider is that the process of preparing specimens for

histologic examination will alter the tissue samples such as

the increased sheering stress from the cutting process and

the dehydration of the tissue during processing and fixa-

tion. The latter impedes full evaluation for the presence of

edema which remains a question in regard to the patho-

physiologic mechanisms of laminitis. It is unclear whether

full histological evaluation of the corium is possible or if

the corium is overlooked during postmortem examination.

Histologically, acute laminitis should display hyperemia,

hemorrhage, marked edema, and occasional thrombosis

within the dermis, and progression of the disease leads to

laminar disorganization and necrosis of the laminar tips

with limited inflammatory cell infiltration.6 This congestion

and edema would explain the changes seen in the corium;

however, upon histologic examination of the corium, there

were no specific differences in vascularity or tissue orga-

nization between normal and laminitic feet.

While all radiographic measurements were characterized

by a significant difference between normal and laminitic

feet, there was a large overlap, illustrated by the fact that

sensitivity for the dorsal hoof wall-to-distal phalanx length

ratio at a cut-off value of 0.3 has a sensitivity of 52% and a

positive predictive value of only 42%. In contrast, the

maximum laminae-to-dermis ratio obtained with MR

imaging has a much more segregated distribution between

normal and laminitic feet with sensitivity of 81% and

specificity of 93–98% depending on which portion of the

foot is measured.

Table 7. Sensitivity and Specificity Using Loss of Laminar Architecturein the Distal, Middle, and Proximal Foot as a Predictor of Histological

Laminitis Using a Categorical Cut-Off Value of 1 and 2

Cut Point Distal Middle Proximal

1Specificity (%) 60.0 72.2 82.8Sensitivity (%) 98.4 93.7 92.1


Table 8. Sensitivity and Specificity Using Loss of Corium Architecture inthe Distal, Middle, and Proximal Foot as a Predictor of Histological

Laminitis Using a Categorical Cut-Off Value of 1 and 2




Table 9. Sensitivity and Specificity Using Altered Laminar Signal Inten-sity in the Distal, Middle, and Proximal Foot as a Predictor of Histo-

logical Laminitis Using a Categorical Cut-Off Value of 1 and 2




Table 10. Sensitivity and Specificity Using Loss of Corium SignalIntensity in the Distal, Middle, and Proximal Foot as a Predictor ofHistological Laminitis Using a Categorical Cut-Off Value of 1 and 2




10 ARBLE ET AL. 2009

The results for all three observers were similar with re-

gard to the subjective ability to make a diagnosis of a

laminitic vs. normal foot using radiographs. The sensitivity

for detecting initial active laminitis was low (47.6–57.2%),

because until there is mechanical breakdown of the lami-

nae, there are no distinct radiographic changes. The spec-

imens that did have radiographic changes may have been in

transition to chronic laminitis.23,24 Horses with radio-

graphic changes are arguably classified as having chronic

laminitis, according to commonly used definitions. For the

purpose of our study, however, this was a continuation of

the same inciting event and was within the initial active

phase. The fact that changes such as laminar separation

may be detected earlier with MR imaging before radio-

graphic rotation and distal displacement occur may neces-

sitate revisiting the definition between acute and chronic

laminitis. Other than laminar separation, there were no

histologic findings to indicate a chronic disease process.

There was a tendency for over-interpreting the MR im-

ages in making a subjective diagnosis of laminitis. Two

factors need to be considered. First, the observers were

only asked to evaluate three out of the 64 total images that

comprised an entire study of the foot. The discontinuity

made reading of each individual image more objective;

however, this prohibited following structures over the

entire length of the foot. Second, the observers were only

given short tutorials on the specific changes they were

detecting, and there are no published observations on what

constitutes expected MR imaging findings in horses with

acute laminitis.

With regard to the Group 2 horses that were at risk for

developing laminitis, only two feet from one horse had

histologic changes characteristic of laminitis. Most likely,

this horse was misclassified because both histologic

and MR imaging changes were diagnostic for laminitis.

Unfortunately, using clinical evaluation to group the

horses introduced another variable. This horse was endo-

toxemic which placed it in the at risk category; however,

the horse was also being treated for a front foot abscess

which has many clinical signs in common with laminitis,

including foot pain, increased hoof wall temperature, and

altered digital blood flow. An abscess was not identified on

necropsy or on MR images, leading us to speculate that the

clinical signs of laminitis were misinterpreted. It then

follows that subclinical laminitis does not produce changes

detectable with MR imaging, or was not present in Group

2 horses. This conclusion is premature given the small

sample size and the limited staining and histologic descrip-

tion in our study.

We recognize that the fine anatomic detail seen at 4.7T is

currently not achievable clinically. However, distinction

between the corium and laminae is possible in magnets that

are used for clinical imaging, and the ratio of the laminae-

to-dermal thickness within the foot and the changes seen

within the corium can be extrapolated. Further work is

necessary to characterize the changes seen with laminitis

when using clinically available magnets. Further study into

the pathophysiologic mechanisms of laminitis will benefit

from studies of live animals, particularly with serial exam-

inations.

In conclusion, alterations in laminar and corium archi-

tecture and signal intensity as well as separation within the

laminae are readily seen at 4.7T and are highly correlated

with a histologic diagnosis of acute laminitis. The sensitiv-

ity of diagnosing laminitis is much higher with high field

strength MR imaging than with radiography. Sensitivity

and specificity are high for predicting laminitis using a

laminae-to-dermis ratio of 0.7. The sensitivity and speci-

ficity of quantitative MR imaging measurements are better

than those obtained by radiography. The sensitivity of

subjective evaluation is higher with MR imaging than with

radiography, and the specificity is likely to improve with

greater familiarity of the MR appearance of the equine

foot. Finally, there was no evidence to confirm the

hypothesis that subclinical changes are present in the soft

tissues of the digit in horses that are at risk for laminitis.

ACKNOWLEDGMENTS

The authors would like to thank Dr. Schmalbrock from the Depart-ment of Radiology, The Ohio State College of Medicine, for her valu-able assistance and expertise and Dr. Wharton from Lexington, KY, forher aid in data collection.

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Table 11. Sensitivity and Specificity Using Separation in the Distal,Middle, and Proximal Foot as a Predictor of Histological Laminitis Using

a Categorical Cut-Off Value of 1 and 2





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MAGNETIC RESONANCE IMAGING OF THE INITIAL ACTIVE STAGE OF EQUINE LAMINITIS AT 4.7 T