Anatomy and Medical Imaging

Architecture of the Infant gluteal muscles: Segmentation of a 3D Model

Supervisor

Ali Mirjalili
Prof. Sue Stott

Discipline

Anatomy and Medical Imaging/Surgery

Project code: MHS013

INTRODUCTION. Anatomically an infant is not a miniature adult. Although gluteal muscles are important in weight bearing and gait, the development of the gluteal muscles architecture have not been studied. One 6 month old formalin embalmed specimen was dissected and digitised (Microscribe® G2X) in situ. 3D models were constructed in Autodesk® Maya® using this data. The architectural parameters, fibre bundle length (FBL), pennation angle (PA) and physiological cross-sectional area (PCSA) were calculated and the infant and adult lower limb muscles compared. Thus, the aim is to determine the segmentation of the 3D reconstruction of the muscles, aponeuroses and tendons of an infant and compare with the adult (previous study) using CT, MRI and MR-DTI.
METHOD. CT, MR proton density and MR-DTI images were acquired from the infant at the Sickkid Hospital in Toronto. The bone surface and the muscles surface will be reconstructed from CT and MR proton density images, respectively. From the MR-DTI images all fibres of the gluteal muscles will be reconstructed using a streamline tracking algorithm. PA and FBL will be estimated using MR-DTI reconstructed. The associated distributions will be compared between the digitied (using Microscribe® G2X) and reconstructed (using DTI images) using the Mann Whitney test.

Skills required: Understanding musculoskeletal anatomy and cross-sectional anatomy

Effect of maternal position on placental circulation and anatomy using MRI

Supervisor

Ali Mirjalili
Alys Clark (ABI)

Discipline

Anatomy and Medical Imaging/Surgery

Project code: MHS014

Recent studies have shown that maternal supine sleep position is associated with an increased risk in late stillbirth (defined as intrauterine death after 28 weeks gestation). When a woman in the third trimester of pregnancy lies in the supine position the gravid uterus compresses major maternal vasculature. This results in reduced blood flow to the maternal placental circulation and may act as an acute fetal stressor. To date there has been very little research looking at the effect of maternal position on placental circulation and anatomy. This area of research is important in understanding the effect of maternal position on fetal wellbeing and will lead to the development of safer sleep practices for women during pregnancy. the aim of this project is to build a 3D model of the placenta in different position (supine Vs Left lateral) using MRI.

3D MRI Atlas of Bottlenose Dolphin Neuroanatomy

Supervisor

Associate Professor Miriam Scadeng
Dr. David Dubowitz

Discipline

Anatomy and Medical Imaging

Project code: MHS109

The brains of dolphins have striking resemblance to humans, in both size and structure, and it would appear that much of their function parallels human function, including language processing. Less is known about the organization of special senses such as the echolocation. The development of a high resolution atlas based on 3D MRI imaging to act as a road map for future studies such as additional diffusion tensor imaging and functional imaging studies is a vital first step to moving the field forward. The MR imaging data for this project has already been acquired and preprocessed, ready for segmentation.
Skills required or to be acquired during the project: in depth knowledge of neuroanatomy (human and dolphin), data segmentation using Amira software. Envisioned outcome: publication of atlas as a paper.

Wright A, Theilmann R , Ridgway S, Scadeng M. Diffusion tractography reveals pervasive asymmetry of cerebral white matter tracts in the bottlenose dolphin (Tursiops truncatus) Brain Struct Funct. 2017 DOI : 10.1007/s00429-017-1474-3

Wright A, Scadeng M, Stec D, Dubowitz R, Ridgway S, Leger JS. Neuroanatomy of the killer whale (Orcinus orca): a magnetic resonance imaging investigation of structure with insights on function and evolution. Brain Struct Funct. 2017 Jan;222(1):417-436. doi: 10.1007/s00429-016-1225-x. Epub 2016 Apr 27. PMID: 27119362

3D Digital Model of Bottlenose Dolphin Anatomy

Supervisor

Associate Professor Miriam Scadeng
Dr. David Dubowitz

Discipline

Anatomy and Medical Imaging

Project code: MHS111

Introduction: Cetacea including dolphins, have striking anatomical and functional resemblances to humans, in both size, and structure, all being air breathing mammals. Indeed the study of dolphin physiology is shedding new light on many human diseases including diabetes and hyperlipidemia, as well as the potential effects of ocean pollution on health.
Dolphins being charismatic icons, are an important species for gaining public interest in the detrimental effects of human activity on the planet. The development of a 3D atlas of dolphin anatomy, that can be distributed to schools and as educational exhibits would be a valuable resource for both the scientific and educational communities. High-resolution 3D CT and MRI data has already been acquired and preprocessed, and is ready for segmentation.
Skills required or to be acquired during the project: in depth knowledge of body anatomy (human and dolphin), and data segmentation using Amira software. Envisioned outcome is publication of atlas as a paper, and distribution of models for education.

Wright A, Theilmann R , Ridgway S, Scadeng M. Diffusion tractography reveals pervasive asymmetry of cerebral white matter tracts in the bottlenose dolphin (Tursiops truncatus) Brain Struct Funct. 2017 DOI : 10.1007/s00429-017-1474-3

Wright A, Scadeng M, Stec D, Dubowitz R, Ridgway S, Leger JS. Neuroanatomy of the killer whale (Orcinus orca): a magnetic resonance imaging investigation of structure with insights on function and evolution. Brain Struct Funct. 2017 Jan;222(1):417-436. doi: 10.1007/s00429-016-1225-x. Epub 2016 Apr 27. PMID: 27119362

Diffusion Tensor Imaging of white matter tracts in Killer Whale: Search for arcuate fasciculus & evidence for complex language

Supervisor

Associate Professor Miriam Scadeng
Dr. Samantha Holdsworth
Dr. David Dubowitz

Discipline

Anatomy and Medical Imaging

Project code: MHS152

The brains of many cetacea have striking resemblance to humans, in both size and structure, and it would appear that much of the function parallels human function. In the bottlenose dolphin we have for the first time delineated a well developed arcuate fasciculus, that appears to be better developed than in any primate except for man. This suggests that the bottlenose dolphin has complex language processing. Based on orca behavior and brain structure we believe that they too have a well developed arcuate fasciculus, and thus complex expressive and receptive language. The MR imaging and Diffusion tensor data for this project has already been acquired and is ready for tractography. Skills required or to be acquired during the project: in depth knowledge of neuroanatomy (human and cetacean), DTI tractograpgy processing. Envisioned outcome: Publication of paper.

Wright A, Theilmann R , Ridgway S, Scadeng M. Diffusion tractography reveals pervasive asymmetry of cerebral white matter tracts in the bottlenose dolphin (Tursiops truncatus) Brain Struct Funct. 2017 DOI : 10.1007/s00429-017-1474-3

Wright A, Scadeng M, Stec D, Dubowitz R, Ridgway S, Leger JS. Neuroanatomy of the killer whale (Orcinus orca): a magnetic resonance imaging investigation of structure with insights on function and evolution. Brain Struct Funct. 2017 Jan;222(1):417-436. doi: 10.1007/s00429-016-1225-x. Epub 2016 Apr 27. PMID: 27119362

Predicting outcomes in health populations

Supervisor

Avan Suinesiaputra
Kat Gilbert

Discipline

Anatomy and Medical Imaging

Project code: MHS194

MESA is a study of approximately 6000 normal volunteers across six cities in the United States. The study was designed to non-invasively look for sub-clinical symptoms of cardiovascular disease. The study is now approaching 20 years of data collection where the full cohort has undergone 2 MRI scans and several rounds of questionnaires and other testing.

Every person has a slightly different shape to their heart. The process of measuring these variation is known as shape atlasing. These atlases allow us to score changes to shape and compare demographic and health information to better understand where the differences in shape come from. Thus far in MESA we have been able to show the differences are seen in smokers, men and women, and those with high blood pressure as well as many other factors.

In this project you will be working with both baseline and follow up data to gather insight into subtle changes in heart shape that occur before an event, and as a result in changes to cardiovascular risk factors. We have shape models for approximately 7000 individual MRI scans which you will use alongside traditional medical measures of heath and demographic data to understand the individual's changes within a population.

Optogenetic modulation of beta amyloid-induced brain network changes in an in vivo Alzheimer`s disease mouse model

Supervisor

Dr Andrea Kwakowsky
Dist Prof Sir Richard Faull

Discipline

Anatomy and Medical Imaging

Project code: MHS121

Alzheimer`s disease (AD). AD is characterized by progressive loss of neurons, memory and other cognitive functions. Currently, there are still no effective treatments to prevent, delay or reverse AD. A feature of the pathogenesis of AD is the increased concentration of neurotoxic soluble oligomers of beta amyloid peptides. Optogenetics is the combination of genetic and optical methods. It uses light-activated ion channels (opsins) for temporal control of neuronal excitability limited to specific selected cell-types mediated by viral vectors and light stimulation that is delivered at a specific brain region; and predicted to be the next generation of deep brain stimulation technology.
The aim of this project is to design an optogenetic stimulation approach to ameliorate beta amyloid-induced changes in neuronal function and behavior in an in vivo Alzheimer`s disease mouse model.

We offer a stimulating and collaborative research environment. The successful candidate will join a lively community of students at the Centre for Brain Research. The ideal candidate is ambitious and highly motivated for pursuing a career in neuroscience.

Skills taught:
-animal handling
-stereotactic brain surgery
-mouse behavioural testing
-neural tissue collection, fixation
-combination of molecular, anatomical and imaging techniques
-data collection, analysis and presentation

Understanding GABA Signalling in the Vasculature of Healthy and Alzheimer’s Disease Brains

Supervisor

Dr Andrea Kwakowsky
Assoc Prof Henry Waldvogel

Discipline

Anatomy and Medical Imaging

Project code: MHS122

Alzheimer`s disease (AD) is characterized by progressive loss of neurons in the hippocampus and cerebral cortex, memory and other cognitive functions. Currently, there are still no effective treatments to prevent, delay or reverse AD. Cerebrovascular dysfunction is strongly associated with the pathogenesis of AD, often significantly preceding the onset of clinical symptoms. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) can regulate vascular function in the brain, controlling vasoconstriction and blood flow – however the mechanisms underlying this are poorly understood.

The aim of this project is to understand how the GABA signaling system regulates vascular function in the human brain and how this function is altered in AD.

We offer a stimulating and collaborative research environment. The successful candidate will join a lively community of students at the Centre for Brain Research. The ideal candidate is ambitious and highly motivated for pursuing a career in neuroscience.

Skills taught:
- neural tissue fixation, processing
- fluorescence immunohistochemistry
- imaging techniques (light and confocal microscopy)
- data collection, analysis and presentation

DARPP32 basal ganglia pathways in the human brain

Supervisor

Henry Waldvogel
Richard Faull

Discipline

Anatomy and Medical Imaging and Centre for Brain Research

Project code: MHS037

This project will suit a motivated neuroscience student who is keen to work on human brain neuroanatomy. It will involve the study of the human basal ganglia, a complex nuclear group in the centre of the brain controlling mood and movement. Degeneration of GABAergic neurons in the striatum, the main input nucleus of the basal ganglia, leads to Huntington’s disease and degeneration of dopaminergic neurons in the substantia nigra leads to Parkinson’s disease. Dopamine is intimately involved in the normal functioning of the basal ganglia and basal ganglia diseases and a key molecule in dopamine functioning is DARPP-32 which is acted on by dopamine and glutamate and leads to the activation of specific basal ganglia pathways. We have found a unique distribution of DARPP-32 in striatal medium spiny neurons in the human brain. This project will define the output pathways of the DARPP-32 cells in the striatum to the globus pallidus and substantia nigra and will be compared with the known pathways. This is a very exciting and novel project in the human brain and will utilise high resolution single, double and triple labelling at light and confocal microscope to determine the precise neurochemical makeup of the basal ganglia pathways in human brain.

Techniques learned:
Human Brain Anatomy
Immunoperoxidase and immunofluorescence immunohistochemistry.
Double and triple immunolabelling for light and laser scanning confocal microscopy.

The project is based on post mortem tissue made available from the Neurological Foundation Douglas Human Brain Bank.

Understanding shape in Transposition of the Great Arteries

Supervisor

Kathleen Gilbert
Avan Suinesiaputra

Discipline

Anatomy and Medical Imaging

Project code: MHS193

Congenital Heart Disease is the most common birth defect, Due to improvements in surgical techniques those with congenital heart disease are living longer, and the population of adults with congenital heart disease is now larger than the pediatric population.

Every person has a slightly different shape to their heart. The process of measuring these variation is known as shape atlasing. These atlases allow us to score changes to shape and compare demographic and health information to better understand where the differences in shape come from. In a study of healthy adults we have been able to show the differences are seen in smokers, men and women, and those with high blood pressure as well as many other factors.

In this project you would work with data collected as part of our atlasing congenital heart disease project. The project will use anonymised images and clinical data from people with transposition of the great arteries to understand the variations in shape with in this diverse population.

Development of cranial nerve components in the chicken embryo

Supervisor

M Fabiana Kubke

Discipline

Anatomy and Medical Imaging

Project code: MHS160

Aims
The formation of the cranial nerves in the developing nervous system depends on a highly coordinated series of events that involves the growth of sensory and motor axons towards their specific targets. While a lot of attention has been paid to the origin of motoneurons and how this relates to the segmental pattern of the hindbrain (rhombomeres), less attention has been paid to how the axons of sensory and motor neurons grow during development to ensure proper connectivity.

This project will examine the development of sensory axons and those of branchiomotor neurons and how these may interact during the formation of mixed cranial nerves.

Skills
Embryonic dissection, embryonic tract tracing, epifluorescent and confocal microscopy, immunocytochemistry, histology.

Building a Brain Machine Interface for song production

Supervisor

M Fabiana Kubke

Discipline

Anatomy and Medical Imaging

Project code: MHS161

Aims
Brain-machine interfaces are used to extract the neural code associated with a behaviour, and use that code to drive a robotic device. In the context of human health, it allows people with motor disabilities to have their brains ‘talk’ directly to a device, such as a prosthetic arm.

We are currently trying to exploit this technology to study how auditory and somatosensory information contribute to the production of speech. We are using a songbird as an animal model because the neural substrates and the process of learning song are similar to those of humans. To separate the processes that are involved in the ‘intention’ to sing from the act of singing itself, we are training birds to learn how to ‘sing’ (through a brain-machine interface) using an audio speaker rather than through their vocal apparatus.

The project involves understanding the models of auditory-vocal learning and vocal production, understanding how vocal motor commands are coded in ‘motor cortex’, how these can be analysed through machine learning algorithms, and animal behaviour analysis.

The organisation of auditory information used for sound localisation

Supervisor

M Fabiana Kubke

Discipline

Anatomy and Medical Imaging

Project code: MHS162

Aims
We know where a sound comes from by comparing the timing of arrival of sound to the two ears. The sensory information that is processed through the cochlea provides no information about where a sound is coming from, so this information needs to be computed by neurons in the brainstem. By studying the delays associated with the transmission of the action potentials from the ears to the brainstem allow the interaural time differences to be translated into a spatial map, we can begin to build models around how sound localisation is made possible by the auditory brainstem circuits.

This project involves learning about the anatomy and physiology of the auditory system, the computational processes that enable sound localisation, the development of software to analyse neural data, and histological tools that answer some questions about the specialisations of neural circuits.

Neuroanatomical basis of tool manufacture

Supervisor

M Fabiana Kubke

Discipline

Anatomy and Medical Imaging

Project code: MHS164

Aims
New Caledonian crows are well known for their ability to manufacture and use tools that are used to obtain food. Neural adaptations that allow this behaviour to occur must therefore exist, but what they remain unknown. This project aims to identify what neural adaptations may have facilitated the evolution of this behaviour and to determine which area/s of the brain are the substrates for this behaviour.

Skills

The project will involve primarily neuroanatomical techniques (histology, immunocytochemistry, 3D brain reconstructions), but the data will be integrated with behavioural data already obtained by Drs Gray and Hunt.

Amplified MRI to understand pathological brain motion

Supervisor

Samantha Holdsworth
David Dubowitz

Discipline

Anatomy and Medical Imaging

Project code: MHS144

Amplified MRI (aMRI) is a new imaging method that magnifies very small motion of the brain as the heart beats. aMRI has shown promise for detecting pathological brain motion due to diseases or disorders that obstruct the brain or block the flow of cerebrospinal fluid. The intension of this project is to investigate whether aMRI can help to visualize abnormal brain physiology. We have preliminary aMRI data acquired on Chiari Malformation I and hydrocepalous patients, obstructive disorders of the brain, which are ready to be processed and analysed. The ideal student for this project would be comfortable with Matlab and be interested in medical imaging and/or image processing. Preference will be given to students with a genuine interest in further postgraduate study.

Modulating chronic inflammation as a potential treatment spinal cord injury

Supervisor

Simon O'Carroll

Discipline

Anatomy and Medical Imaging and Centre for Brain Research

Project code: MHS106

Background
Spinal cord injury (SCI) effects between 130 and 180 New Zealanders each year and has a devastating impact not only on patients but on their families as well. SCI usually manifests due to initial trauma characterized by massive cellular loss, both neuronal and glial, in addition to blood brain barrier permeability. Following the initial injury, secondary injury can occur both in the acute and chronic phase. The chronic phase of injury is characterized by a lasting inflammatory response which leads to the development of neuropathic pain and is inhibitory to axonal regeneration.
Connexin 43 (Cx43) is a protein which forms gap junctions, allowing transfer of molecules between cells. After injury it can also form a hemichannel (half channels) directly to the extracellular space and release proinflammatory mediators directly to the extracellular space and promoting an inflammatory environment. Cx43 hemichannels are open in the tissue following spinal cord injury and play in role in the damage spread.

Project
We have previously shown that pharmacological inhibition of Cx43 hemichannels in acute rat SCI models has shown efficacy in reducing the inflammatory levels and conferring an increased motor ability compared to controls. We now know that Cx43 levels remain high in chronic injury. Few studies have looked at the chronic inflammatory and the inhibition thereof. Given that Cx43 is a validated target, we are trialling a Cx43 hemichannel blocking drug to determine if it can reduce chronic inflammation. This project will use immunohistochemistry in rat spinal cord tissue to determine if our treatment can reduce inflammation. This work has potential to ultimately make a real difference for people living with spinal cord injury, through reducing neuropathic pain and potentially allowing for axonal regeneration and recovery to occur.

Skills learnt:
Immunohistochemistry
Histology
Fluorescence Microscopy
Report writing
Clinical interaction (during the project there will be an opportunity to visit the Auckland Spinal Cord Rehabilitation Unit)

Super-resolution imaging of primary cilia

Supervisor

Sue McGlashan
David Crossman
Sophia Leung

Discipline

Anatomy and Medical Imaging

Project code: MHS119

Cells are exquisitely sensitive to the physical signals experienced in their tissue environment. Seminal studies have shown that varying the rigidity or stiffness of external cell culture surfaces can be used to as stimulus for the development of stem cells into either neurons, bone or muscle cells. However, although how cells ‘feel’ these changes remains poorly understood. Our group is examining the cells’ own sensory probe called the primary cilium is controlled by the mechanical stiffness of the extracellular matrix. To fully understand this, we need to dig deeper into understanding how the structure of the cilia change during these interactions.

Super-resolution imaging is a relatively new type of microscopy that allows imaging down to 30 nm resolution (compared to 200nm on a regular fluorescent microscope). We will use the only system available in New Zealand (based in the Dept of Physiology) to optimise super-resolution imaging of primary cilia and associated cellular structures. The project will involve immunohistochemically labelling, cell culture, super-resolution imaging and image analysis. The overall goal is to optimise labelling of primary cilia in cultured cells and in some tissues if possible (e.g. brain, heart and cartilage) to provide a robust and reproducible method for all researchers in this faculty to examine cilia in their model system.

Come and join our super friendly and social lab group for a summer of multi-coloured nano-scale imaging that will blow your mind!

Understanding the link between osteoarthritis, inflammation and obesity

Supervisor

Dr Ashika Chhana
Dr Sue McGlashan

Discipline

Anatomy and Medical Imaging

Project code: MHS070

Background: Osteoarthritis is the most common arthritis affecting over 60% of all New Zealanders. Recent reports have suggested that the lack of successful drug therapies is due to generalised patient selection, which doesn’t reflect the complexity of osteoarthritis and the multiple osteoarthritis sub-types. To achieve targeted patient treatment, the clinical and cellular characteristics of each osteoarthritis sub-type must be fully defined. Obesity is a major risk factor for osteoarthritis and is associated with chronic low-grade inflammation. How joint tissues are affected during osteoarthritis progression in obese patients compared to healthy-weight patients is still unknown in humans; understanding this process is necessary to fully characterise the obese osteoarthritic phenotype.

Research Objectives: The overall goal of this project is to investigate if articular cartilage from obese patients with clinically diagnosed osteoarthritis shows differences in disease progression and characteristics as a result of the chronic inflamed state associated with obesity. Specifically, human cartilage obtained from obese and healthy-weight patients with osteoarthritis will be assessed for differences in (i) extracellular matrix structure and degradation patterns; (ii) basal secretion levels of inflammatory mediators; and (iii) gene expression profiles.

The aim of this summer studentship will be to assist and perform one or more these assessments.

Potential Skills Taught:
- Basic research methods
- Immunohistochemistry and histology
- Protein quantification (ELISA)
- Image and data analysis