Carbon nanotube field emission based imaging and irradiation technology development for cancer research and treatment

Transcription

1 Carbon nanotube field emission based imaging and irradiation technology development for cancer research and treatment Sha Chang 1 and Otto Zhou 2 Dept. of Radiation Oncology 1 and Physics & Astronomy 2 University of North Carolina Medical School

2 Outline Carbon nanotube field emission technology CNT-based imaging systems (available) Micro-CT Mammography tomosynthesis Gantry-mount IGRT CNT-based irradiation systems (development update) Single cell irradiation Micro-RT (irregular field and IMRT) Future directions

3 Carbon nanotube (CNT) & field emission (1-50nm in diameter, ~1-10μm long tube) CNT e- e- e - Electric field (not heat) controlled electron emission.

4 Basic structure of CNT cathode e - e - e - e - Gate electrode Insulator Substrate Variable voltage power source Carbon nanotube film Ultra-high current: 2000 A (8cm source)

5 Today s X-ray technology - >100 year old technology - High operating temperature - Large size - Slow response time - Limited resolution - Single pixel Rotating anode tube Siemens direct cooling tube

6 Key advantages of CNT x-ray technology High temporal resolution Multi-pixel source array Schematic of the prototype CNT field emission multi-pixel microbeam array.

7 Small animal research technology Challenges: improve temporal resolution, better physiological gating, faster scanning time, lower dose, better contrast weight (grams) breaths /minute heartbeats / minute Human Rat Mouse 70,

8 CNT Micro-Focus Field Emission X-Ray Source for in-vivo imaging of small animal cancer models um resolution, 0-50kVp, 1-3mA tube current, ms pulse width

9 CNT field emission imaging technologies Single source micro-ct Cyclops 1.0 Charybdis 1.0 J. Zhang et al (2005)

10 UNC dynamic micro-ct scanner Charybdis 1.0 J. Liu et al./zhou Lab/ Appl. Phys. Lett. 2006; G. Cao et al, SPIE Medical Imaging 2008

11 Respiratory gated μct imaging (free-breathing anesthetized mice) (a) (b) (c) (d) Expiration Inspiration -12lp/mm at 10% MTF --50ms temporal resolution peak (0.48ml) base (0.53ml) G. Cao et al. SPIE Medical Imaging 2008; G. Cao et al. Phys Med Biol 2009

12 Cardiac gated μct imaging Reconstructed slice images show clear difference between systole (a) and (c), and diastole (b) and (d) in the axial and coronal views of a mouse heart, respectively

13 Detection of Vascular Calcification Proximal aortic arch

14 CNT FE multi-pixel x-ray imaging Source Array Stationary CT Stationary Tomosynthesis Micro-RT Single Cell Irradiation Source Array Subject Detector IGRT Detector

15 X-ray digital breast tomosynthesis (DBT) The digital mammogram on the left shows 1 calcification. Slices from the tomosynthesis reconstructions, shown in the 2 right images, show that one calcification is at 30 mm height in the breast, and the other at 47 mm. (From Hologic) Sha_chang@med.unc.edu

16 UNC Argus 2.0 : Stationary DBT Expected benefit: faster scanning time, better resolution, simpler design, lower imaging dose

17 Nanotube Stationary Tomosynthesis (NST) (Siemens) Maltz, et al Med Phys 36 (5), May 2009 Artiste 52 x-ray sources: 4 banks and each has 13 sources Each x-ray source is individually controlled ~ 5 sec. imaging acquisition time for tomosynthesis and less for multiple projection imaging A single portal imager is used Imaging during treatment!

18 CT NST Coronal Slice 1 Region of better resolution Coronal Slice 2

19 CNT-based irradiation technology development Update

20 CNT FE based x-ray pixel beam micro-rt Micro-CT-RT (b) Prototype (a) micro-rt 4.0cm x 2D x-ray pixel beam array z y Multi-array system Single array system Sha_chang@med.unc.edu

21 X-ray pixel beam array micro-rt Individual pixel beam control for irregular field shaping and IMRT micro-rt planning by micro-plunc micro-ct-rt integration for fractionated IGRT. 6-pixel beam field Pixel beam: 2mm

22 CNT micro-rt dosimetry (MC simulation) 2mm XPBA 1cm field

23 Tumor (a) Prototype CNT micro-rt system X-ray pixel beam (1-2 mm) 5x10 pixel array Pixel beam size: 2mm 1Ebergy: 100kV Dose rate: 1Gy/min. (b) Pillar (ceramics,φ 12.5mm) Collimator (Cu) Anode (25.4 um W foil) Electron beam size at anode: 325 um Distance: 12 mm (Focusing electrode-anode) Focusing electrode (Stainless steel plate: 2mm) Spacer (Glass or Ceramics: 3 mm) Gate (φ 25.4 um wire W mesh + 1 mm stainless steel plate) Cathode (CNTs on Cr plus Cu layer) Spacer (Glass: um) SiO 2 +Si Radiation Oncology Assembled micro-rt. Physics & Astronomy

24 Image of prototype of multi-pixel micro-rt

25 Cathode chip design and fabrication 5 x 5 5 x 10 Electrical connection pads CNT cathodes Sha_chang@med.unc.edu

26 Pixel beams are individually addressable 50 irradiation beams on Selected 10 irradiation beams on Electronic circuit

27 This function results in electronical shaping of tumor field for irradiation Irradiation beams obtained by individually controlling Six pixel-beam field To electronically form tumor shape for irradiation through turning on a sub-set of the x-ray pixel beams.

28 NCI irradiation pattern by electron and x-ray beams through individual controlling of cathodes Electron pixel beams image 2mm Energy: 30kV Image from micro-rt x-rays measured by GAFCHROMIC film.

29 CNT Multi-pixel micro-rt development Challenges: High voltage is technically challenging to achieve in academic research labs; High current (high dose rate) needs forced anode cooling; Need industry s involvement after feasibility demonstration. Next Steps: CNT based micro-ct-rt integration.

30 Single pixel microbeam device UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL AAPM 2006 Orlando Chang (30)

31 SCI dose and dose rate calibration Dose is controlled by the number of emission current pulses; Estimated dose rate range: cgy to 10 4 Gy per sec! FWHM = 28 μm Dose rate: 10 3 Gy/sec!! 20 μm Measured by GAFCHROMIC film Emission current: 2 μa; frequency: 100Hz; duty cycle: 5x10-4 UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL AAPM 2006 Orlando Chang (31)

32 Cell irradiation demonstration (H2AX: DNA damage) (rat fibroblast cells) Neg. control 23Gy, 30keV electron beam pos. control

33 Multi-pixel Film Irradiation and Dosimetry 50 µm FWHM: 40 um, dose: 29.1 Gy 1.45mm Film Irradiation from 5x5 cathode array locations with all pixels interconnected UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL AAPM 2006 Orlando Chang (33)

34 SUMMARY Carbon nanotube field emission X-ray technology is capable of ultra-high temporal resolution imaging/irradiation and novel multi-pixel source array systems; CNT field emission based novel imaging systems (micro-ct, Tomosynthesis IGRT, stationary breast tomosynthesis), and irradiation systems (micro-rt, multi-pixel single cell irradiation) are feasible; Industry involvement is essential to realize the full potential of the technology (Xintek, Xinray, Siemens).

35 ACKNOWLEDGEMENTS Researcher team: Sigen Wang, Jerry Zhang, David Bordelon, Jared Snider, Eric Schreiber, Adrienne Cox, et al. NIH-U54-CA (Cancer Nanotechnology Center of Excellence grant) NIH-NIBIB (4R33EB004204) NIH-NIBIB (4R33EB S1) NIH-NCI (R21 CA )* NIH (R21 CA )* North Carolina Biotechnology Center* UNC Lineberger Comprehensive Cancer Center Department of Homeland Security (TSWG) Xintek Inc. (UNC start-up company) *: Irradiation device grant