Week 4 part 1 Flashcards
What is the role of biomarkers?
Molecules that indicate the presence of a disease of dysfunction
Increasing instrumental for confirming diagnoses
Choosing the best treatments
Monitoring disease progression
What does biomarker help with?
- Care
2. Financial
What are most biomarkers?
Metabolic
Many years we have biomarkers for liver disease, diabetes
Where are neurological biomarkers present?
- Cerebrospinal fluid
Rarely - or at undetectable levels - in blood
What does the BBB shield the brain from?
Harmful substances circulating in the bloodstream
What does CSF sampling require?
Invasive and painful lumbar puncture procedure
What did technological advances in detection increase in?
- Sensitivity
e. g. Simoa-single-molecule array/miRNA analysis
Used in labs and CSF to detect very low level compounds
For diagnostic purposes, what did the barrier do?
Made the grains chemistry inaccessible to a convenient blood test
What is the benefit of greater sensitivity ?
Earlier detection of biomarkers for disease
What is development of CTE?
Accumulation of many subconcussive impacts to the brain
What can Quanterix measure?
Biomarkers in blood
E.g. neurofilament light - a biomarker for neuronal damage that indicates head trauma
What can larger biomarker signatures be detected with?
Technology from CDI laborarotories
Offers microarrays of functional human proteins to test antibodies present in human liquid biopsy samples such as blood, serum, plasma, CSF or tissue lysates
What are biomarkers signature detected with?
Panels of high-quality antibodies
What can biomarkers be used to study,
How immune system deals with dead brain tissue after a stroke
What does the immune system remove?
Dead brain tissue after a stroke by a process known as liquefactive-necrosis
What can be used to detect biomarkers?
Multiplexed immunoassay
The prevalence of neurological disorders
- Growing at a very high pace
- Biomarkers are expected to play a vital role in better understanding of the disease and development of personalised medicine specific to the patient
What are the different types of biomarkers in the market?
- Genomic Biomarker
- Proteomic Biomarker
- Metabolomics Biomarker
- Imaging Biomarker
What holds a higher market value that teachers over US $ 2,700 Mn by the end of 2025?
- Genomics Biomarker
Genomics to the Biomarkers market
Efficient process of examining a disease at the genetic level
Play a major role in the drug development and personalised medicine too
What plays a crucial role in successful management of disease?
Early diagnosis of neurological disease
What does neurological system have?
Limited accessibility
Makes diagnosis of disease a difficult process
What does available diagnostic procedure lack in?
- Sensitivity
2. Specificity for evaluation of disease progression and prognosis
What are neurological disorders diagnosed with?
- Cognitive testing
- Clinical history
- Structural MRI
- Neurological examination
What is Biomarker considered as?
- Indicator in evaluation and measurement of a pathological and physiological process
- Indicator for pharmacological response to treatment
What is there a high demand for in the market?
- Identifying and validating biomarkers from a large number of population
- Conducting the research process with the help of this method
Why is imaging relevant for clinics and pharma?
- Provide accurate and reliable functional and anatomical information with minimal physiological interference
- Allows real-time, high-resolution imagine (quantitative and qualitative analysis)
- Longitudinal studies for imaging disease progression and respond to therapy in real-time
What is an ideal scanner for imaging modalities?
- High resolution/ sensitivity
- FOV for the whole body scanning-speed of acquisition fast
- Versatile (dynamic scan, gating, ease of use)
What is used for animal research/medical research?
Optical imaging
What are the challenges for preclinical imaging between animal/human brain?
- Size
2. Anatomical/structural resolution in animal is a challenge
What are the challenges for preclinical imaging?
- restrain the animals
- To minimise stress and improve reproducibility
- Profound effect on animal physiology
What does MRI use?
Protons found in the body
What does the protons spin to create?
A strong magnetic charge
What happens when a strong magnetic field is introduced in MRI machine?
H+ aligns in that field
What does radio frequency pulse introduced disrupt?
H+ into 180 degree realignment with a magnetic field
What happens when radio frequency pulse is turned off?
H+ realign with the magnetic field releasing electromagnetic energy
What is MRI able to detect?
Energy and differentiate various tissue based on how quickly they release energy based in once pulse is turned off
What is the consequence of manipulation of H+?
Releases energy
This every gives you MRI image
What is MRI a versatile system to look at?
Soft tissue
What are the applications of MRI?
- Excellent contrast soft tissue
- Very versatile: anatomical and metabolic data
- Main diagnostics clinics
- Spatial resolution ~100um
- No exposure to radiation
What are the critical issues of MRI?
- Very specialised and costly equipment
2. High resolution may require High magnetic field and long acquisition time
Why is contrast agent important?
- Indicates something abnormal
- Associates to brain damage
- Inject IV the thing leaks and foes into the brain
- Very useful and commonly used
What is Diffusion Tensor Imaging (DTI)?
- Relatively new imaging technique
- Evaluate white matter in the brain
- The orientation and direction of white matter tract can be visualised and quantified
- quantifying the orientation and directional uniformity of water diffusion in brain tissue
In white matter of DTI, what is the nobility of water restricted in?
Directions perpendicular to the axons oriented along the fiber tracts
The orientation and direction of these fibers can be traced
Why is DTI used?
To evaluate the orientation and asymmetry of white matter giver tracts in patients diagnosed with schizophrenia
What is X-day and CT scan principally used as?
Structural methods
What does X-rays have?
Short wave-lengths that can pass through most tissues in the body
What does bones contain and are able to stop?
- Calcium
2. Stop some of the X-rays and can form a shadow
What can X-rays directed at body produce?
- shadows on the opposite side that can be registered on film
- Bones are clearly visible whilst soft-tissues are shadowy
- 3D reconstruction of bone architecture
What is derived from X-ray that allows 3D imaging?
- CT scan
CT scan
- Deriving from X-day
- Provide a 3D reconstruction of tissue
- High resolution for imaging bones (10um)
What is the application of CT?
- Gold standard for qualitative and quantitative skeleton assessment (2D and 3D)
- Co-registration if anatomical data with other modalities (functional/ molecular data)
What are critical issues of CT scan?
- Radiation exposure
- Long time acquisition (for high res)
- Like soft tissue construct but improved with exogenous contrast agents
What is CT imaging limited by?
Poor constrast between soft tissues
What does bone scintigraphy use?
Radioactive material to bone diseases (2D)
What does SPECT/PET provide?
High detection sensitivity
High resolution 3D localisation of the radionuclide agent
What is SPEC/PET imaging good for?
- Functional information (molecular level) on onset and progression of a given biological process and/or disease
What is the application of SPETC?
- Tomographic functional imaging (p-mmol)
- High spatial resolution and good sensitivity
- Higher availability of clinical SPECT tracers and in house
What are the critical issue of SPETC?
- Exposure to gamma radiation
- Injection of radiotracers
- Long half life: monitoring during decay period
What does SPETC detect,
Single emission of the radioactive agent in the body
Detected via detectors
What are the two ways to have light?
- Have light purely as emitted as an optical source
2. Excitation
What is Bioluminescent Imaging (BLI)?
- Uses a natural light-emitting protein such as luciferase to trace the movement of certain cells
- Identify location of specific chemical reactions within the body
- Applied to both gene expression and therapeutic monitoring
What is Fluroescence imaging?
- Uses endogenous or exogenous molecules or materials that emit light when activated by external source such as laser
- An external light of appropriate wavelength is used to excite a target molecule, which then fluoresces by releasing longer-wavelength, Lower-energy light
What is optogenetics?
Emerging technique that combines genetic recombination and optics to control neurons structure and function
How does optogenetic work?
- A light-sensitive Gene is inserted into the host organism
- Light-sensitive gene activation is triggered by laser lights of specific wavelength
- Fine control of timing of a neurons firing, researchers can activate or inhibit a signal, allowing for key insight into birth normal and abnormal brain function
- Neurons can be turned on or off with incredible precision
5.
What is the application of optogenetics?
- Identifying neural identity
- Number of neurons associated to specific network activity
- Determine which spatiotemporal patterns of activity casually drive behaviour (neuronal code)
Photo acoustic imaging?
- Non-ionising laser pulses are delivered into biological tissues
- Some of the delivered energy will be absorbed and converted into heat
- Leading to transient thermoplastic expansion and thus wideband - ultrasonic emission
