A MRI-compatible stereotaxic localizer box enables high-precision stereotaxic procedures in pigs

Bjarkam, Carsten Reidies; Cancian, Graziano; Larsen, Mette Krogh; Rosendahl, F.; Ettrup, Kaare S.; Zeidler, D; Blankholm, A; Østergaard, Leif; Sunde, Niels; Sørensen, Jens Christian

doi:10.1016/j.jneumeth.2004.05.004

Cited by 52 publications

(37 citation statements)

References 14 publications

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“…Though the inversion recovery sequence is superior in visualizing the GP [49] , the exact location of the two GP segments in the minipig has yet to be specifically studied using histological data. Based on the analysis of the individual and mean MRI and comparison with anatomical atlases of large nonprimate mammals [15,50,51] , we hypothesize that the minipig brain has both an external GP forming the lentiform nucleus with the putamen and an entopeduncular nucleus located more ventrally in close proximity to the internal capsule. Felix et al [22] and Yoshikawa [51] have studied the GP on Nissl-stained slices of the Landrace pig and have identified two connected segments, an anterior ventrolateral segment and posterior dorsomedial segment [50,51] .…”

Section: Discussionmentioning

confidence: 99%

“…There are several key structures in the basal ganglia that can be targeted in the context of PD including: the subthalamic nucleus (STN), the putamen, the caudate, the substantia nigra (SN), the pedunculopontine nucleus and the globus pallidus (GP) [24][25][26][27][28][29][30] . Targeting of these structures in the minipig has been aided by the development of a stereotactic head frame that was custom built to fit the minipig skull [15] . The accuracy of preoperative targeting can be limited by the lack of sufficient structural information in standard MRI acquisitions.…”

Section: Introductionmentioning

confidence: 99%

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Defining the Intercommissural Plane and Stereotactic Coordinates for the Basal Ganglia in the Göttingen Minipig Brain

Rosendal

Chakravarty²,

Sunde³

et al. 2010

Stereotact Funct Neurosurg

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The intercommissural line joining the anterior and posterior commissures defines stereotactic coordinate systems used in functional neurosurgical procedures. Such coordinate systems are generally accepted in humans and nonhuman primate experimental settings and provide high stereotactic precision and reproducibility. The ethical concern surrounding the use of nonhuman primates has motivated and helped popularize the use of the Göttingen minipig as an alternative experimental model for experimental functional neurosurgery. We investigated the position and variability of the intercommissural line in the minipig brain using in vivo MRI. From these data, standard coordinates for the minipig basal ganglia were estimated. We found the variability of the intercommissural line to be small in the Göttingen minipig and the variability of the basal ganglia structures to the mid-commissural point to be minor.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Defining the Intercommissural Plane and Stereotactic Coordinates for the Basal Ganglia in the Göttingen Minipig Brain

Rosendal

Chakravarty²,

Sunde³

et al. 2010

Stereotact Funct Neurosurg

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“…The Göttingen minipig has gained increased interest during the last decade as a non-primate large experimental animal, also including its use as an animal model in PD (Mikkelsen et al 1999;Danielsen et al 2000;Sørensen et al 2000;Watanabe et al 2001;Dall et al 2002;Bjarkam et al 2004Bjarkam et al , 2005Bjarkam et al , 2008aDalmose et al 2004Dalmose et al , 2005Lind et al 2007;Lindvall and Wahlberg 2008;Jensen et al 2009;Rosendal et al 2009). For further refinement and use of the animal model in PD research, detailed knowledge of the SNc is crucial.…”

Section: Discussionmentioning

confidence: 99%

“…Its gyrated brain is large (6 9 5 9 4 cm) compared with rodents, with a great subcortical anatomical resemblance to primates (Felix et al 1999;Larsen et al 2004;Bjarkam et al 2008b;Rosendal et al 2009). The large brain enables PET and MRI scanning procedures as well as conventional neurosurgery, stereotaxic neurosurgery and surgical implantation of devices intended for human use Sørensen et al 2000;Watanabe et al 2001;Dall et al 2002;Bjarkam et al 2004Bjarkam et al , 2005Bjarkam et al , 2008aDalmose et al 2004;Lindvall and Wahlberg 2008;Jensen et al 2009;Rosendal et al 2009). The pig genome resembles that of primates (Lind et al 2007); the pig is affordable compared with primates, and many of the ethical considerations combined with using primates as experimental animals may be avoided (Goodman and Check 2002), making it possible to include more animals in studies, and thereby hopefully obtain more valid results.…”

Section: Introductionmentioning

confidence: 99%

The substantia nigra pars compacta of the Göttingen minipig: an anatomical and stereological study

2009

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Parkinson disease (PD) is a neurodegenerative disorder resulting from progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Despite advances in medical and surgical therapies, many PD patients experience progression of their symptoms and medical side effects over time. To explore new treatments, new animal models mimicking the progressive PD nature are needed. The pig is well suited for this purpose with its large gyrated brain, sensitive to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The objective of this study was to provide the anatomical foundation for such a model, describing in detail the SNc in normal Göttingen minipigs and estimating the volume and total number of tyrosine hydroxylase (TH)-positive neurons. The brain stems of 6 Göttingen minipigs were paraffin embedded and serially cut before Nissl staining and immunohistochemical visualization of TH. The volume of the SNc and the total number of TH-positive neurons were estimated by design-based stereology. The substantia nigra was located at the dorsal rim of the crus cerebri extending throughout the mesencephalon. A dorsal pars compacta and a ventral pars reticulata were demonstrated. The SNc merged with the ventral tegmental area medially and the retro-rubral field dorsocaudolaterally. The total number of TH-positive neurons in the SNc unilaterally was estimated to 80,700 [74,100;87,300], and the volume estimate was 26.4 mm(3) [25.0;27.8]. We conclude that the anatomy of the SNc in the Göttingen minipig corresponds well with that of higher primates, and is well suited for further studies aimed at optimizing this non-primate large animal model for PD.

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“…The pigs were ventilated with a mixture of 50% O 2 and 50% air, and isoflurane (1-2.5%). The pigs were placed prone in an MRI-compatible stereotactic localizer box [18] ( fig. 2 A).…”

Section: Surgical Proceduresmentioning

confidence: 99%

Safety and Function of a New Clinical Intracerebral Microinjection Instrument for Stem Cells and Therapeutics Examined in the Göttingen Minipig

Bjarkam¹,

Glud²,

Margolin³

et al. 2009

Stereotact Funct Neurosurg

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Background: A new intracerebral microinjection instrument (IMI) allowing multiple electrophysiologically guided microvolume injections from a single proximal injection path in rats has been adapted to clinical use by coupling the IMI to an FHC microTargeting Manual Drive, designed to be used with standard stereotactic frame-based systems and FHC frameless microTargeting Platforms. Methods: The function and safety of the device was tested by conducting bilateral electrophysiologically guided microinjections of fluorescent microspheres in the substantia nigra of 4 Göttingen minipigs. Results: The device was easy to handle and enabled accurate electrophysiologically guided targeting of the substantia nigra with minimal local tissue damage. Conclusion: The IMI is suitable for clinical use and may prove useful for various stereotactic procedures that require high levels of precision and/or three-dimensional distribution of therapeutics within the brain.

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A MRI-compatible stereotaxic localizer box enables high-precision stereotaxic procedures in pigs

Cited by 52 publications

References 14 publications

Defining the Intercommissural Plane and Stereotactic Coordinates for the Basal Ganglia in the Göttingen Minipig Brain

Defining the Intercommissural Plane and Stereotactic Coordinates for the Basal Ganglia in the Göttingen Minipig Brain

The substantia nigra pars compacta of the Göttingen minipig: an anatomical and stereological study

Safety and Function of a New Clinical Intracerebral Microinjection Instrument for Stem Cells and Therapeutics Examined in the Göttingen Minipig

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