5. The evolution of bio-imaging
Weissleder and Pittet. Imaging in the era of molecular oncology. Nature 2008
6. Microscopy & Optical imaging
The human eye can focus from 20cm to
infinity control illumination and resolve to
±100 m however it can’t magnify
The Nimrud Lens
Babylon750-710 BC
The British Museum
7. Molecular Biology
Genomics
Proteomics
Metabolomics
The ‘omics’ is very trendy today in daily science
8. Molecular Biology
Translation
DNA mRNA Proteins Metabolites
±25000 genes ±500000 Nx107 Nx106
Transcription
Effect of the environment (life style)
Genomics
Gene
≠
Proteomics Blueprint
Metabolomics
9. The evolution of bio-imaging
Weissleder and Pittet. Imaging in the era of molecular oncology. Nature 2008
10. The Bridge
Small Animal Imaging
Molecular Biology Medical Imaging
11. The evolution of bio-imaging
Weissleder and Pittet. Imaging in the era of molecular oncology. Nature 2008
12. In the beginning there was …
Wilhelm Röntgen 22 December 1895 23 January 1896
Nobel Prize Physics 1901 Hand of Anna Berthe Hand of Albert von Kölliker,
Discovery of X-rays a famous anatomist
13. … the first medical image ?
The hand of a 12-year-old boy who had shot
himself one month before his hand was
examined by x-rays in 1896 at at Columbia
University.
14. … the first medical image ?
Find Fight Follow
Up
Diagnosis Treatment Follow-up
The hand of a 12-year-old boy who had shot
himself one month before his hand was
examined by x-rays in 1896 at at Columbia
University.
15. The medical imaging timeline
Weissleder and Pittet. Imaging in the era of molecular oncology. Nature 2008
16. The medical imaging timeline
1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010
X-ray CT
MRI
Fiber optics
SPECT
PET
17. The medical imaging timeline
1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010
X-ray CT
MRI
Fiber optics
SPECT
Find Fight Follow
Up PET
Diagnosis Treatment Follow-up
28. Imaging Analogue: Functional imaging
Carrier or Agent Label
Specific moiety Moiety for detection
Moiety for localization of specific process Moiety for imaging signal
37. The role of molecular biology
Genomics Cancer
Proteomics Alzheimer
Metabolomics CAD
38. Biomarkers
The FDA defines a biomarker as, "A characteristic that is
objectively measured and evaluated as an indicator of normal
biologic processes, pathogenic processes, or pharmacologic
responses to a therapeutic intervention".
Agent
Optical label (in vitro)
Radioactive label (in vivo) Target
41. MICAD
List contains today 5076 items !!
Probably not complete
Only 236 FDA Approved
From which 123 Discontinued
Thus 113 still available
47 SPECT and PET Tracers
3357 SPECT and PET tracers
(66%)
47 FDA Approved
42. Biomarker development
Multi-disciplinary
R. Weissleder, B.D. Ross, A. Rehemtulla, S.G. Gambhir (Eds.), Molecular Imaging: Principles and Practice.
43. Biomarker development
In-vitro
In-vivo
R. Weissleder, B.D. Ross, A. Rehemtulla, S.G. Gambhir (Eds.), Molecular Imaging: Principles and Practice.
44. Biomarker development
Cellular / Molecular level Cell culture
Molecular Biology
In-vitro
Preclinical imaging
Clinical imaging
In-vivo
Human Small animal
45. Small animal imaging
70 kg 250 g
280x smaller in volume
±6.5 times smaller / direction
1 mm 150 µm
46. Small animal imaging
70 kg 20 g
3500x smaller in volume
±15 times smaller / direction
1 mm 66 µm
49. Small animal imaging
Disease Progression
imaging
quantitative parameters
therapy
Response to Therapy
50. Small animal imaging
Modality Study time Resolution Intrinsic Probe Dynamic Radiation Cost
Contrast Sensitivity Imaging Dose
SPECT 30-90 min 0.5-2 mm None <pM Yes 10-100cGy 700K
PET 5-60 min 1-2 mm None <pM Yes 10-100cGy 700K
MRI ±60 min <100 µm High µM - mM Yes - 1M
CT 10-15 min <200 µm Low mM No 10-20cGy 350K
US ±60 min <100 µm Low ? Yes - 200K
BLI ±5 min ±1 cm None nM Yes - 250K
FLI ±5 min <5 mm Variable nM No - 150K
NIR ±10 min <5 mm None pM No - 250K
Multi-modality imaging