Imaging program UBC and TRIUMF V Sossi, PhD Physics and Astronomy PET Director UBC A. Jon Stoessl, CM, MD Professor & Head, Neurology Co-Director, Djavad Mowafaghian Centre for Brain Health
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Imaging program UBC and TRIUMF
V Sossi, PhD
Physics and Astronomy
PET Director
UBC
A. Jon Stoessl, CM, MD
Professor & Head, Neurology
Co-Director, Djavad Mowafaghian Centre for Brain Health
Brain illness
§ Brain illness (neurological disorders, mental illness and addiction) is the major health challenge in the 21st century with a socio-economic cost greater than cancer and cardiovascular disease combined amounting to approximately 40% of the global burden of disease ($60B/yr in Canada).
§ There is currently no disease modifying treatment.
2012 Brain Canada report
o ~85 brain research-related laboratories - clinics, basic science, genetics, physics and engineering
o ~ $40M in CFI infrastructureo 150 researcherso 1 Canada Excellence Research Chair, 28 Canada Research Chairs,
16 Donor funded Chairs, 7 Donor funded Professorshipso > $20M annually of research funds
Clinical and translational research in Parkinson’s, Alzheimer’s, Mood disorders; Mental health and addiction; Stroke; Neurotrauma; Multiple sclerosis; Genetics; Neuroimaging
Djavad Mowafaghian Center for Brain Health (DMCBH) -2013
Brain Research at UBC (UBC strategic priority)
Multimodal neuroimaging key component of UBC DMCBH
• Hybrid PET/MRI (CFI 2017 Sossi $13.7M)• 3T MRI + EEG (CFI 2015 Mackay $5.9M)• Future MEG
§ The first PET/MR in Canada dedicated exclusively to brain research§ First GE PET/MRI§ ~ 3 other centers in the world with the same breadth in brain research
Background: PET program at UBC/TRIUMF
§ Established in ~ 1980 as partnership between TRIUMF and the UBC Pacific Parkinson’s Research Centre
TRIUMF (E. Vogt)Instrumentation
(PETTVI built at Triumf, J Rogers)
Radiochemistry(T Ruth, M Adam)
UBC Imaging and medical research: Pacific Parkinson’s Research Centre (PPRC) (D Calne)
PET Director (B Pate – UBC)
Evolution: PET program at UBC/TRIUMFUBC - Imaging
Clinical programs• Parkinson’s (main focus, Stoessl)
• Dementia
• Mood disorders
• Clinical trials
• Multiple sclerosis
Preclinical program
Physics (PET Quantification algorithms Kinetic
modeling, PET/MRI image analysis methods)
Scanners• Siemens HRRT (CFI T Ruth
• GE Advance (CIHR)
• Siemens microPET (CFI Ruth)
• Milabs Vector (CFI Sossi)
PET Director (T Ruth – TRIUMF)
TRIUMF - Isotope production and Radiochemistry
acquisition of a dedicated TR13~ 15 radiotracers routinely
produced
Acquisition of GMP capable
chemistry equipment
P Schaffer, radiochemistry, TRIUMF V Sossi, Imaging UBC
Funding (since 2003): > $55M – research funds
Publications(since 2003): > 400
Evolution (ctn’d): PET and PET/MRI (2018)
program at UBC/TRIUMF
SIGNATM
PET/MR -60cmOutperform with the power ofnext-generation1 PET/MR
1. Compared to a non-digital PET detectorContact Us (/en/about_us/contact_us)
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Overview
Shatter diagnostic boundaries
The SIGNA PET/MR combines the power of 3.0T with the next generation of PET technology.
The innovative SIGNA PET/MR features 3.0T magnetic resonance (MR) technology integrated with GE’s latest positron emission
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Imaging: UBC
Radiochemistry: TRIUMF
§ Immediate GMP production capabilities crucial
§ $1.3M UBC contribution to the upgrade of TR13-related lab 007 to GMP standards
High impact publications from UBC PET program
¤ Zimprich et al., Neuron 2004 – 1595
¤ Olanow et al., Ann Neurol 2003 – 908
¤ Lang et al., Ann Neurol 2006 – 572
¤ Whone et al., Ann Neurol 2003 – 547
¤ De la Fuente-Fernandez et al., Sceince 2001 –525
¤ Lee et al., Ann Neurol 2000 – 353
¤ Marks et al., Lancet Neurol 2008 – 332
¤ Calne et al., Nature 1985 – 310
¤ De la Fuente-Fernandez et al., Brain 2004 -236
¤ Liu et al., Lancet Neurol 2018
¤ Perez-Soriano et al., MovDisord 2017
¤ Wile et al., Lancet Neurol 2017
¤ Kordower et al., Ann Neurol2017
Novel research enabled by PET/MRI
§ Brain energetics§ Metabolic and functional networks incl. neurotransmitters§ Neurovascular coupling§ Multi-modal disease and treatment efficacy biomarkers
PET/MRI at UBC DMCBHWide ‘end user’ base supported by instrumentation, analysis and technical expertise
o Better understand disease mechanism
o Identification of treatment targets
o Optimized treatment strategies
Brain energetics (production and use of energy in the brain)
§ Related to mitochondrial function
§ Mitochondria – “cellular power plants” generate most of adenosine triphosphate (ATP), main source of chemical energy
§ Participate in maintaining ‘cell health’ and signalling
§ Alterations found contributing to neurodegeneration.
§ Very difficult to measure in-vivo
A possible measuring technique
Cerebral metabolic rate of oxygenCerebral metabolic rate of glucose
=CMRO2
CMRGlu
In presence of mitochondrial dysfunction
Both decrease, but CMRO2 decreases more
Advanced MRI
FDG PET
CMRO2
CMRGlu
PET/MRI at UBC Synergy and cross-fertilization between applicants and research areas
Abnormal brain energetics and connectivity
Healthy aging (Liu Ambrose)
PD(Stoessl, Mckeown,Sossi)
AD and dementiaHsiung
Multiple sclerosisTraboulsee
Mood disordersYathamAddiction
Clark
neuroprotectionAbnormal brain energetics and connectivity
Abnormal brain energetics and connectivity
Abnormal neurotransmitter release and connectivity
Abnormal neurotransmitter release and connectivity
Abnormal neurotransmitter release and connectivity
Abnormal protein aggregation Abnormal protein aggregation
Inflammation
InflammationInflammation
Abnormal brain energetics and connectivity
+ Algorithms(Mackay, McKeown, Sossi,Wang)
UBC needs from TRIUMF
§ GMP -compliant tracer development
§ Implementation of new (at least new to us) tracers
§ Reliable tracer delivery
§ As disease understanding progresses, novel molecular targets are identified (LRRK2, a- synuclein, inflammation, etc)
§ Opportunity of collaborations with SFU (Vocadlo), UBC(Perrin) and other academic sites
§ Ability for rapid translation into human use§ Optimization of tracer production§ Development of novel multi-modal probes § Opportunity of joint commercial activities
Synergistic opportunities for TRIUMF
UBC provided leverage: basic science and imaging expertise, access to animal models and suitable patient populations
Projected importance of brain imaging in brain illness managemento Neurodegeneration precedes
clinical symptoms by many years
o Optimal therapeutic window may be very early
o Imaging likely to be used to identify disease as soon as a treatment becomes available
o PET and possibly rsfMRI may be best positioned for early detection
Imaging will become diagnostically very relevant
UBC and TRIUMF have an opportunity to lead § research§ clinical trials § establishment of a province-wide standard of clinical
case for brain illness as soon as treatments become available.
Wile et al., Lancet Neurol 2017
TSPO in CISGianetti et al., Brain 2015
Key requirement
Investment into radiotracer development, production and delivery – IAMI!
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