1. Spine and spinal cord pathologies and among the most complex medical issues to
treat. Spine disorders, particularly back pain, are a leading cause of healthcare
expenditures in the US, costing over $100 billion annually. Compounding this
problem is an age-associated increase in the prevalence of spine disorders.
Currently, rats are used as the primary animal model for spinal cord research.
These models have helped researchers elucidate some mechanistic and
physiologic aspects of spine pathologies, however, translatable clinical results
have been very limited. A better model for spine research is needed for
researchers to discover and validate new effective treatments readily translatable
to humans. Swine are commonly used in medical research for their many
anatomical, physiological, and metabolic similarities to humans. More recently,
swine is becoming a favored model for spinal cord injury research, due to human-
like congruency with respect to spine and spinal cord anatomy, vasculature,
immune responses, and functional assessments. In the current study, we show
that Wisconsin Miniature Swine™ (WMS) is especially relevant as a model for
human spinal cord pathology and is also practical for use as a platform for
developing therapeutic delivery technologies, like convection enhanced delivery
(CED). WMS, while retaining all of the advantages swine generally have as a
medical model, also have the advantage of remaining at a normal human weight
when fully grown. We show that WMS spine, in comparison with conventional
swine, is a superior choice for relevant translational spine research.
Our results suggest WMS are useful for chronic longitudinal studies, acute
pathologies such as trauma, and platform device development. We also highlight
the potential use for WMS spine model to develop CED technology.
Introduction
Contusion spinal cord injury
Conclusion
Swine spine source
Ten frozen WMS spines were obtained from the Department of Animal Sciences,
University of Wisconsin, Madison, WI for this study. Domestic WMS were 5-6
months-old and had an average weight of 50 kg. Five cadaver WMS spines were
used for the anatomy experiment and five cadaver WMS spines were used for the
infusion experiment.
Anatomical dimensions of the WMS spine
For the anatomy experiment, extraneous tissue was removed from five spines and
total length including process height and vertebral spacing was measured (A).
Each vertebra was then individually dissected and additional measurements were
taken. We compared this with the human vertebrae as referenced by the study by
Busscher et al., (2010)5 (B). Measurements were taken with digital calipers
between anatomical landmarks of the vertebrae. Pedicle height and width were
measured for each pedicle (right and left) along with measurements of each of the
transverse processes (right and left). The spinous process length was measured
in regard to the sagittal midline of the vertebrae. The total length of the spine was
measured from C1 through L6 (C1-C7, T1-T15, L1-6). The cervical lordosis was
measured as the angle between the upper end-plate of C3 and the lower end-
plate of C7, thoracic kyphosis between the upper end-plate of T1 and the lower
end-plate of T15, and lumbar lordosis was measured as the angle between the
upper end-plate of L1 and the lower end-plate of L5 or L6, respectively.
Intervertebral disc height was measured in the central mid-point of the disc.
Infusions and injections
Injections of bromophenol blue (50 uL over 15 seconds) were made into 5 WMS
spines through the superior intervertebral space with a 0.28G needle and BD
syringe at 6 locations (C2, C6, T2, T6, T10, and L2). A total laminectomy was then
performed on the spine WMS cadavers and the spinal cord removed.
Approximately 30 minutes after injection, measurements of dye diffusion were
taken by 2 independent observers. In a separate experiment, India ink was
delivered to a Bottle Nose swine ventral spinal cord ex vivo via percutaneous
delivery (C).
Wisconsin Miniature Swine™ as an Anatomic Model for the Human Thoracic Spine and Development of Therapeutic Delivery Technologies
Patricia Stan*a, Abhishek Chopra*a, Dominic T. Schomberga,b, Seah Buttara, Steve Dobek, Naomi Yutuca, Gurwattan S. Miranpuri*a, Daniel K.
Resnick,a Dhanansayan Shanmuganayagam.a,c
* Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA 53792
* * Biomedical and Genomic Research Group, University of Wisconsin- Madison, WI
Results
Acknowledgements
Future Directions
15.00
17.00
19.00
21.00
23.00
25.00
27.00
29.00
31.00
T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 T13 T14 T15
Comaprison of Human and WMS Vertebral Body Height Dimensions
VBHa WMS VBHa H VBHp WMS VBHp H
15.00
17.00
19.00
21.00
23.00
25.00
27.00
29.00
31.00
T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 T13 T14 T15
End Plate Dimensions
UEPW UEPD LEPW LEPD
6.00
8.00
10.00
12.00
14.00
16.00
18.00
20.00
T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 T13 T14 T15
Spinal Canal Dimensions
SCW SCD
0.00
5.00
10.00
15.00
20.00
25.00
T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 T13 T14 T15
Processus Dimensions
TPL R/L PedH R/L Ped W R/L
10.00
20.00
30.00
40.00
50.00
60.00
70.00
80.00
90.00
T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 T13 T14 T15
Spinous Processus Length
1.50
1.70
1.90
2.10
2.30
2.50
2.70
2.90
3.10
T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12
Lengthincm
Intravertebral Measurements
35
45
55
65
75
85
95
C2 C6 T2 T6 T10 L2
Distanceinmm
Injection Location
Distance of BPB diffusion 15 - 45 minutes after 50 uL
injection with 0.28G needle (0.36mm)
Vertebral Dimensions
Spinous Processus Length and Angle Infusions and Injections
Dissected Spinal Cord of WMS: Measurements from C5, C6, T1-T13, L1, L2, L3 and from
C4 - C6, T1-T13, L1- L6.
Characterizing measurements and tissue properties in WMS model.
WMS spine length (583.7 mm +/- 21.5) is comparable to humans (569.4 mm) and porcine (569.5 mm).
Vertebral Body Height Dimensions
WMS VBHa values (20.2-23.5 mm) compared to human values (17.3-25.6 mm) (Busscher et al. 2010).
Human thoracic spine has a wider range of VBHa data compared to the swine spine; both spines are
comparable at T4-T11. WMS VBHp values (18-25mm) compared to human values (18.8-28.5mm),
(Busscher et al. 2010).
End Plate Dimensions
Upper and lower end plate depth values (16.59-18.59mm) were compared to larger human spine end
plate values. The ratio of LEPW in WMS is similar to that in humans (Bozkus et. al., 2005).
Spinal Canal Dimensions
WMS spinal canal values of depth (9-13.3) and width (13.8-16.9mm) are less wide and deep than
human values (Bozkus et al., 2005). The human spinal canal narrows T2-T8 then widens from T9-T12
(Kumar et al. 2000). The WMS spinal canal narrows from T1-T3, T4-T15 and deepens from T3 – T15.
Transverse Processus Length
SPL showed no true trend. The lengths rose from T11-T15, but varied greatly from T1-T10.
Pedicle Width and Height (Right and Left)
The pedicle heights differed between human specimens and our WMS specimens with the WMS
specimen having a higher mean pedicle height (Sheng et al., 2010).
Spinous Processes Length
Spinous processes length indicated a decreasing length from T1-T15. The spinous process length
trends downward in WMS, whereas in humans, the spinous process trends downward from T3 – T12
(Kumar et al. 2000).
Spinous Processus Length, Angle, and Intravertebral Measurements
Intravertebral measurements varied, but generally trended upwards. SPA decreased (T1-T8) then
increased (T9-T15).
Infusions and Injections
The high standard deviation indicates that the high rates of diffusion in cervical and thoracic are
inconclusive. Therefore, lumber, cervical, and thoracic have similar diffusion patterns.
Whole spine measurements
A
B
Spinal cord delivery of India ink
in a porcine model via
percutaneous
delivery.
A) Resulting external anatomy of
the infused spinal cord. B) Soft
tissue CT quality image obtained
with robotic biplane angiography
system C) Bone and hardware
images demonstrating the
approach to the spinal cord and
subsequent D) delivery into the
ventral spinal cord target.
C
We propose that the WMS will be a suitable model to develop novel SCI treatments and
delivery devices, such as convection enhanced delivery (CED) (Miranpuri et al., 2013).
We will adopt porcine traumatic thoracic spinal cord injury (Lee et al., 2013). The ability to
inject into specific spinal cord regions would allow for exploration of new therapies
requiring targeted delivery and minimizing side effects due to therapeutic interaction
outside the desired region. Our lab is currently developing technology capable of
delivering therapeutics directly to targeted areas of the SC under MRI guidance with
minimal surgical intervention. To develop minimally invasive targeted therapies, a precise
surgical delivery system targeting specific regions of the SC must be created using an
appropriate translational animal model that allows rapid assessment of clinical relevance
of new therapies. The swine model fulfills many of these important parameters. This work
will enable us to apply CED technology to pig models in vivo, an essential step to
translating any medical treatments to patients.
Validating efficacy of the currently used convection enhanced delivery (CED) model and
demonstrating a non-invasive method for drug distribution will provide sufficient steps
needed to use this platform in vivo. We will design, fabricate, and test a hardware platform
that (1) can be stably mounted to the spine under a MIS procedure, (2) is MRI compatible,
and (3) accommodates the introduction and remote guidance of an injection catheter. Our
research will impact the consequences of SC injury to potentially improve recovery,
functional deficits, sensory dysfunction, and pain through the creation of a novel
therapeutic delivery system.
Objectives
Individual Vertebral
Measurements
Vertebral Body Height Anterior VBHa
Vertebral Body Height Posterior VBHp
Upper End-Plate Width UEPW
Upper End-plate Depth UEPD
Lower end-plate width LEPW
Lower end-plate depth LEPD
Spinal Canal Width SCW
Spinal Canal Dimensions SCD
Transverse Processus Length TPL
Spinous Processus Length SPL
Spinous Processus angle SPA
Pedicle height (Average right and left) PedH
Pedicle Width (Average right and left) PedW
Methods
• To accurately measure WMS thoracic vertebrae dimensions
• To compare the anatomical dimensions of WMS spine vertebrae with the
human spine
• To measure infusion distances that can later be compared to that of
humans.
Porcine Thoracic Injury Behavioral Scale (PTIBS).
FIG. 2. Custom designed weight drop impactor
2. (A) Weight drop impactor. (From left to right)
the guide rail attached to the
articulating arm and trigger system, drop weight
(50 g), static weight (100 g) and measure rod
with pre-set distance. (B) Impactor
mounted on the animals after weight drop injury.
After the weight (50 g) was dropped, an
additional 100 g static weight was added for
5 min. (Lee et. al., 2013)
0
20
40
60
80
100
120
140
160
0
1
2
3
4
5
6
7
T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 T13 T14 T15
MeanAngleinDegrees
Cm
Spinous Proccessus Length and Angle
SPL SPA
1) Vertebral Dimensions – taken
from 5 WMS spine cadavers
2) Spinous Processus Length
and Angle – taken from 5
WMS spine cadavers
3) Infusions and Injections –
distance traveled through
WMS spinal cord