Week 1 Flashcards

1
Q

What is a positron?

A

A positron is a particle of matter with the same mass as an electron but an opposite charge. It is a form of antimatter because, when a positron encounters an electron, the two completely annihilate to yield energy. Its not the same as a proton!

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2
Q

What theory and by whom led the evolution of modern physics?

A

Special Relativity by Albert Einstein.

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3
Q

What is special relativity?

A

Special relativity is an explanation of how speed affects mass, time and space. The theory includes a way for the speed of light to define the relationship between energy and matter — small amounts of mass (m) can be interchangeable with enormous amounts of energy (E), as defined by the classic equation E = mc^2.

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4
Q

What is general relativity and how does it differ from special relativity?

A

Special relativity applies to all physical phenomena in the absence of gravity. General relativity explains the law of gravitation and its relation to other forces of nature. It applies to the cosmological and astrophysical realm, including astronomy.

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5
Q

How special relativity explains Mario and Luigi’s disagreement?

A
  • All is relative including time, so they are both correct.

- Simultaneity is not absolute - it depends on the observer.

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6
Q

What does the Bohr’s hydrogen model say?

A

Bohr model of the atom. In the Bohr model of the atom, electrons travel in defined circular orbits around the nucleus. The orbits are labeled by an integer, the quantum number n. Electrons can jump from one orbit to another by emitting or absorbing energy.

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7
Q

What was the shortage of the Bohr’s model?

A

It did not explain why a charged particle, the electron can stay in orbit around nucleus of opposite charge, the proton without crashing into nucleus itself.

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8
Q

What was Paul Dirac input?

A

He described quantum wave functions, that were added to De Brogile’s model relativistic effects.

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9
Q

What were 2 predictions from Dirac’s equation?

A
  1. Charged particles have a property of spinning (rotating around their axis).
  2. As charged particles they generate a magnetic field:
    * certain strength
    * certain direction

Water protons are the magnetic moment and basic principle behind MRI.

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10
Q

How does the water protons behave in terms of magnetic fields?

A

Generally they are directed randomly, resulting in null magnetization. However when the strong magnetic field is switched on, the spins will align to the direction of that magnetic field, and will spin with a rotating speed that will be dependent on the intensity of that magnetic field.

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11
Q

What are the four main components of MRI?

A
  1. Strong magnetic field.
  2. Gradient coils. These are magnetic fields that change linearly along X, Y, Z axes so that each point in the field of view has a slightly different magnetisation, hence different spinning frequency.
  3. Radio frequency coil that emits pulses. These pulses will excite the protons as long as the frequency of the excitation is the same as the one of the rotating spins. This excitation pulse will send the spins into a different state so that the net magnetisation resulting from all the spins will form an angle of 90 or 180 degrees with the direction of magnetic field.
  4. Radio frequency detector. Note that each spin in a different location will send a signal with very specific radio frequency.
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12
Q

What happens after the pulse is switched off?

A

The water protons will go back to their initial state, which means that their magnetisation decay back to what was before. The rate depends on the tissue the water protons are in.

By collecting these magnetic decays, at different frequencies, which correspond to different locations, a computer program will generate maps of magnetic relaxations, MRI images.

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13
Q

What is tractography and what for its used?

A

In neuroscience, tractography is a 3D modeling technique used to visually represent nerve tracts using data collected by diffusion MRI. It uses special techniques of magnetic resonance imaging (MRI) and computer-based diffusion MRI. The results are presented in two- and three-dimensional images called tractograms.

Diffusion tensor imaging tractography, or DTI tractography, is an MRI (magnetic resonance imaging) technique that measures the rate of water diffusion between cells to understand and create a map of the body’s internal structures; it is most commonly used to provide imaging of the brain.

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14
Q

What is angiography?

A

Magnetic resonance angiography–also called a magnetic resonance angiogram or MRA–is a type of MRI that looks specifically at the body’s blood vessels. Unlike a traditional angiogram, which requires inserting a catheter into the body, magnetic resonance angiography is a far less invasive and less painful test. Uses paramagnetic agents such as gadolinium.

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15
Q

What other molecules apart from water protons can give a magnetic resonance?

A

Creatinine, Choline, N-acetylaspartate produce resonance, and these can be explored using MRI radiofrequency signal to explore not space, but different molecular resonances.

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16
Q

What is heamoglobin?

A

It is the protein in blood that brings around oxygen to the peripheral tissues where oxygen is released.

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17
Q

What is BOLD effect? How it works?

A

Blood oxygenation level dependent. It depends on paramagnetic properties of hemoglobin.

Oxygen bound hemoglobin or not bound, changes its paramagnetic properties, hence difference in oxygenation can be readily imaged. Since oxygen consumption increases when a piece of brain tissue is particularly active, we can use BOLD effect to visualise brain functional activity when a subject performs a task in a scanner.

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18
Q

What is antimatter?

A

Antimatter, substance composed of subatomic particles that have the mass, electric charge, and magnetic moment of the electrons, protons, and neutrons of ordinary matter but for which the electric charge and magnetic moment are opposite in sign.

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19
Q

Who found positron in 1993?

A

Carl Anderson at Caltech lab.

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20
Q

What is unique about positron?

A

It is generated by nuclear reaction by proton - rich nuclei. It survives a little after expulsion from the nucleus. It is slowed down by interactions with other particles until it finds a slow moving electron and anihilates (destroy) it, emitting two gamma photons. Gamma photons have a lot more energy than X-ray that instead are generated by electrons.

This is unique because electron-positron anihilation is the only known reaction whereby mass is entirely converted to energy. (wow).

21
Q

How PET works?

A

Positron emitter isotopes such as O15, C11, F18 can now be produced by local cyclotrons and attached to any substrate (drug, sugar, etc) and injected in to humans. The concentration of radioisotope would be small, but because it can pick up so much energy it can be visualized by a ring detectors that stop gamma radiation.

22
Q

What is a biomarker?

A

A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. or any biological characteristic that can objectively measured.

In definition there are always 2 things to be mentioned: biological target and a quantitative measure.

23
Q

In what ways you can classify biomarkers?

A
  1. Simple (body temperature) or complex (genetic test). This is usually checked to see susceptibility of an individual to a certain disease.
  2. They can also be divided depending on invasiveness:
    * Invasive: biopsy - for stating diagnosis such as cancer and hepatitis.
    * invasive: blood/urine - for investigating presence of infection.
    * non-invasive: imaging scans like X-ray for broken bones and internal trauma.

Each biomarker has a specific purpose in different situation, hence needs to be carefully selected.

24
Q

What is Diabetes mellitus? How its biomarkers evolved during the time?

A

It is a disease characterized by an excess of sugar in the urine. in 16th century two Indian physicians developed a diagnostic test with ants. They were able to identify a disease by testing whether ants were or not attracted by patient urine. Famous London physician Thomas Willis in 1660 found the new method - urine tasting.

25
Q

How are biomarkers classified based on areas of application?

A
  1. Clinical use (tools/technologies for understanding, prediction, cause, diagnosis, progression, regression)
  2. Pharmaceutical industry (testing new drugs, treatments, clinical trials).
26
Q

How biomarkers are classified in clinical research?

A
  1. Biomarkers of risk

2. Biomarkers of disease

27
Q

What does the biomarker of risk measure?

A

The risk to develop certain disease, therefore used before the disease sets in.
It includes measurements of exposure to environmental risks factors (toxic agent) or genetic susceptibility tests. Both tests are quantitative, non-exclusive (more than one biomarker can be used in a combined test, and not necessarily linked to the disease aetiology.

28
Q

What are the limitations of risk measuring biomarkers?

A

ApoE4 in AD is strongly associated with the disease, but:

  • there are patients without ApoE4, who develop AD
  • there are healthy individuals with ApoE4

Some risk factors are difficult to measure. Environment stress for example.

29
Q

What for biomarkers of disease are used? 3 types of tests.

A

In the presence of a disease or condition.

  1. Screening tests. Used before manifestation of the symptoms.
  2. Diagnostic tests. Follow manifestation of the symptoms and used to confirm or exclude presence of a certain disease.
  3. Prognostic tests. Predict clinical outcome or drive treatment decision. Also used to reduce heterogeneity in clinical trials.

It is worth to note that disease is not an on/off status. it is a progression of causal cascades of events. Some biomarkers are able to monitor this cascade directly. Others only reflect indirectly.

30
Q

What are imaging biomarkers?

A

Biomarkers that use imaging as a measurement probe.

31
Q

What are the two advantages of imaging biomarkers?

A

Allow non-invasive in vivo access of:

  1. Functional and
  2. Structural biological characteristics.

Functional imaging modalities are more appealing than structural ones, because they predict better pathological mechanisms of the brain disease. Also some of the brain disease does not produce structural changes in early stages.

32
Q

What are three pathological features of Alzheimer’s disease?

A
  1. Brain atrophy, particularly in the medial temporal lobe.
  2. Extracellular deposition of beta-amyloid containing plaques.
  3. Intracellular accumulation of neurofibrillary tangles containing hyperphosphorylated Tau proteins.
33
Q

Which three parts of the brain make up the medial temporal lobe?

A

Hippocampus, amygdala and parahippocampal regions, and is crucial for episodic and spatial memory. MTL memory function consists of distinct processes such as encoding, consolidation and retrieval.

34
Q

What for is the structural MRI biomarkers used?

A

mainly to detect presence of atrophy across the whole brain or in some particular brain regions as hippocampus or the brain cortex.

Hippocampal atrophy is a signature of AD that reflects the memory loss of a patient.

35
Q

What for the functional MRI is used?

A

f-MRI and magnetic resonance spectroscopy has been used to measure connectivity loss of neuronal decline at different stages of the disease.

36
Q

What for the molecular imaging or the PET is used?

A

It has been used to investigate alteration of glucose metabolism or beta-amyloid accumulation.

37
Q

Why not to use all different biomarkers at the same time?

A

Because each of the biomarker is showing different aspects of the disease, and these do not necessarily occur at the same time.

38
Q

What is psychiatric disorder?

A

It is a behavioral or mental pattern that may cause suffering or a poor ability to function in life.

39
Q

Why diagnosis in mental illnesses is based on symptoms?

A

because there is a lack of understanding of the biological mechanisms to drive these conditions.

40
Q

What is endophenotypes?

A

Objective characteristics used to separate behavioral symptoms into more stable phenotypes with a clear genetic connection.

41
Q

What are the two types of variability in statistical performance of biomarkers?

A
  1. Intra-subject variability: variability of a given measure within the same subject.
  2. Inter-subject variability: variability of a given measure between different subjects.
42
Q

What are the sources of variability in statistical performance of biomarkers?

A
  1. Technical: experimental design, confounding factors, measurement error.
  2. Biological: intrinsic variability of the process.
43
Q

What are the two main parameters for assessing a biomarkers capacity to identify the biological process of interest?

A
  1. Sensitivity

2. Specificity

44
Q

What does the sensitivity indicate?

A

Sensitivity indicates the proportion of positives that are correctly identified as such.

45
Q

What does the specificity indicate?

A

Specificity indicates the proportion of negatives that are correctly identified as such.

46
Q

What other characteristics describe biomarkers performance?

A
  1. Accuracy

2. Positive and negative predictive values

47
Q

What is prevalence and why it is important?

A

It is the proportion of the disease found to be affecting a particular population.
It has an impact on positive and negative predicted values. By reducing the prevalence of disease, we notice an increase of negative predictive value and dramatic reduction of positive predictive value. This happens, because false positives become much more likely than the true positive cases.

48
Q

What is the ROC curve?

A

The ROC curve shows the trade-off between sensitivity (or TPR) and specificity (1 – FPR). Classifiers that give curves closer to the top-left corner indicate a better performance. As a baseline, a random classifier is expected to give points lying along the diagonal (FPR = TPR).

49
Q

What two processes are involved in validating new biomarker?

A
  1. Validation: the process of assessing the measurement performance characteristics (accuracy and precision).
  2. Qualification: the process of providing evidence to link a biomarker with the biology and hence a clinical endpoint.