MOIRA (MOlecular Imaging with RAdionuclides) F. Garibaldi, gr. Coll. Sanita What: Design (and implement) a SPECT detector with submillimeter spatial resolution.

MOIRA (MOlecular Imaging with RAdionuclides)

F. Garibaldi, gr. Coll. Sanita’

What: Design (and implement) a SPECT detector with submillimeter spatial resolution and adequate sensitivity suitable for molecular imaging of biological processes “in vivo” Why: Detect vulnerable atherosclerotic plaques in mice and stem cells distribution monitoring (infarction)

It sets forth to It sets forth to probe the molecular probe the molecular

abnormalitiesabnormalities that are the that are the basis of diseasebasis of disease

rather rather than to image than to image the end effectsthe end effects of of

these molecular alterations.these molecular alterations.

The rat and mousemouse host a large number of human diseases. Therefore one can study disease progression and therapeutic response under controlled conditions.

Molecular imaging : the Molecular imaging : the in vivoin vivo characterization and measurement of biologic processes at the cellular and molecular characterization and measurement of biologic processes at the cellular and molecular level.”level.”

Coronary hearth disease is a leading cause of death in western countries.

Injuries are generated by unstable plaques.

No way to detect the nature of plaques with standard techniques (angiography).

The identification & treatment of vulnerable atherosclerotic plaques prior to rupture has great impact in health care

PET (microPET) cannot attain the needed performances!

Increases apoptosis (programmed death cell) occurs in vulnerable plaques compared to stable plaque of the same size

Atherosclerotic vulnerable plaques

imaging apoptosis by proper tracer (e.g. 99Tc-HYNIC-Annexin-V) that binds to apoptotic cells

Simulations show that arrays of CsI(Tl) 0.6 x 0.6 mm2 coupled to H9500 PSPMT’s Hamamatsu (or Burle MCP(smaller “anode pixel size”) or LaBr3 continuous are the best options.

Individual channel readout at 10-20 KHz (1024 to 8192 channels) Coded apertures

collimators

Spatial resolution: ~ 500 m (~ minimum plaque size)

Sensitivity : 10 cps/Ci

Area single module : ~ 10x10 cm2

We would like to build 1 detector out of 8 or one module out of 4

Submillimeter spatial resolution already obtained

(FWHM=0.93 mm)

AND

High sensitivity (~850cps/MBq)

Both spatial resolution and

sensitivity should be further improved

Sensitivity 10 times smaller than required

pinhole 0.5 mm

Simulations show that arrays of CsI(Tl) 0.6 x 0.6 mm2 coupled to H9500 PSPMT’s Hamamatsu or LaBr3 continuous are the best options.

Readout has to be able to acquire individual channels at rates 10-20 KHz (1024 to 8192 channels)

Submillimeter spatial resolution already obtained with pointlike source.(FWHM=0.93 mm)

Hign sensitivity (~850 cps/MBq)

(factor ~ 30 with respect to the pinhole and 6 with respect to parallel hole)

Coded apertures collimators

Pinhole - multipinhole

Improve both spatial resolution and sensitivity

MOIRA (MOlecular Imaging with Radionuclides)

“… “… the the in vivoin vivo characterization characterization and measurement and measurement of biologic of biologic

processes at the cellular processes at the cellular

and molecular leveland molecular level.” (Weissleder, .” (Weissleder, RSNARSNA 2000) 2000)

It sets forth to It sets forth to probe the molecular abnormalitiesprobe the molecular abnormalities that are the that are the

basis of diseasebasis of disease ratherrather

than to image than to image the end effectsthe end effects of these molecular alterations. of these molecular alterations.

Imaging of specific molecular targets enables:Imaging of specific molecular targets enables:

earlier detection and characterizationearlier detection and characterization of disease; of disease;

earlier and directearlier and direct molecular molecular assessmentassessment of of treatmenttreatment

effects;effects;

more fundamental understandingmore fundamental understanding of disease processes. of disease processes.

The rat and mousemouse host a large number of human diseases

Opportunity to study disease progression / therapeutic response under controlled conditions

non-invasively and repetitively in same animal

And reasonable FOV

Very difficult. It does not exists in the “market” With PET one cannot attain this s.r. moreover with SPECT there is more variety of molecules

MOIRA (MOlecular Imaging with RAdionuclides)

F. Garibaldi, gr. Coll. Sanita’

What: Design (and implement) a SPECT detector with submillimeter spatial resolution and adequate sensitivity suitable for molecular imaging of biological processes “in vivo” Why: Detect vulnerable atherosclerotic plaques in mice and stem cells distribution monitoring (infarction

It sets forth to It sets forth to probe the molecular probe the molecular

abnormalitiesabnormalities that are the that are the basis of diseasebasis of disease

rather rather than to image than to image the end effectsthe end effects of these of these

molecular alterations.molecular alterations.

-The rat and mousemouse host a large number of human diseases. Therefore study disease progression and therapeutic response under controlled conditions non-invasively and repetitively in same animal ca be made

Molecular imaging : the Molecular imaging : the in vivoin vivo characterization and measurement of biologic processes at the cellular and molecular characterization and measurement of biologic processes at the cellular and molecular level.”level.”

Coronary hearth disease is a leading cause of death in western countries. Injuries are generated by unstable plaques

PET (microPET) cannot attain the needed performances!

Motivation: The identification & treatment of vulnerable atherosclerotic plaques prior to rupture has significant impact in health care Hypothesis- increased apoptosis (programmed occurs in vulnerable plaques compared to stable plaque of the same size Goal- to prove the hypothesis in a transgenic mouse model using SPECT imaging techniques

Investigate stem cells ability to regenerate injured tissue by monitoring in vivo migration and homing (infarction) fo several days. Postmortem tissue analysis are presently the main tool to investigate such process.

Aterosclerotic vulnerable plaques

Stem cells

Caratteristiche insufficienti per lo studio di processi biologici in piccoli animali

quindi

Sensitivity very important

Coded apertures System Resolution = 1.7 mm; Sensitivity = 10361 cpm/μCi @ 40 cm

Parallel hole; LEHRSystem Resolution = 15.2 mm; Sensitivity = 1063 cpm/μCi @ 10 cm

Diffusione di cellule staminali (CD34+) in topo

Fig. 19 Clinical PET scanner vs coded apertures

Testa di topo con diverse risoluzioni spaziali

HamamatsuH8500 PS-PMT

NaI(Tl) (pixellated; 1.2

pitch)

MURA 14 masks

High FoV, 1.1 mm pitch

High Resolution, 0.7 mm pitch

Si è visto che con rivelatore di dimensioni 50 x 50 mm2 è possibile ricostruire le immagini in un DOF ‘ragionevole’. L’uso di un rivelatore più grande (100 x 100 mm2) consente una maggior flessibilità.

Si possono usare maschere diverse, con numero di buchi maggiore e quindi più efficienti o con buchi più piccoli e quindi miglior risoluzione spaziale.

Si costruiranno due maschere con caratteristiche diverse (maggiore efficienza o migliore risoluzione spaziale)

Reconstruction of a 122 keV point-like source

using the coded apertures

Submillimeter spatial resolution

(FWHM=0.93 mm)

Hign sensitivity (~850 cps/MBq)

(factor ~ 30 with respect to the pinhole and 6 with respect to parallel hole)

Uptake ratio 6:1

12 x 12 mm² Tumor

Uptake ratio 6:1

8 x 8 mm² Tumor

Uptake ratio 6:1

5 x 5 mm² Tumor

Uptake ratio 6:1

3 x 3 mm² Tumor

Uptake ratio 12:1

12 x 12 mm² Tumor

Uptake ratio 12:1

8 x 8 mm² Tumor

Uptake ratio 12:1

3 x 3 mm² Tumor

Source-Background Uptake ratio 12:1

5 x 5 mm² Tumor

High gain in SNR, tumors smaller than 5 mm visible? (rough simulation)

tumor 12 x 12 mm² uptake 1:12 (at 54.7 mm)phantom DoF thickness(36.4 mm)

SNR = 100 ± 4SNR = 65 ± 3 SNR = 51 ± 3

artifacts

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3D Simulation

measurement