Today's X-ray technology. Siemens direct cooling tube. Rotating anode tube. - >
100 year old technology. - High operating temperature. - Large size.
Carbon nanotube field emission based imaging and irradiation technology development for cancer research and treatment Sha Chang1 and Otto Zhou2 Dept. of Radiation Oncology1 and Physics & Astronomy2 University of North Carolina Medical School
Outline z z
Carbon nanotube field emission technology CNT-based imaging systems (available)
Micro-CT Mammography tomosynthesis Gantry-mount IGRT z
CNT-based irradiation systems (development update)
Single cell irradiation Micro-RT (irregular field and IMRT) z
Future directions
Carbon nanotube (CNT) & field emission
(1-50nm in diameter, ~1-10μm long tube)
CNT
eeeeeee-
Electric field (not heat) controlled electron emission.
Basic structure of CNT cathode Gate electrode
e- e- e- eInsulator
Variable voltage power source Substrate
Carbon nanotube film Ultra-high current: 2000 A (8cm source)
Today’s X-ray technology -
Siemens direct cooling tube
>100 year old technology High operating temperature Large size Rotating anode tube Slow response time Limited resolution Single pixel
Key advantages of CNT x-ray technology z
High temporal resolution
z
Multi-pixel source array
Schematic of the prototype CNT field emission multi-pixel microbeam array.
Small animal research technology Challenges: • improve temporal resolution, • better physiological gating, • faster scanning time, • lower dose, •better contrast
Human
Rat
Mouse
weight (grams)
70,000
250
25
breaths /minute
12
85
120
heartbeats / minute
60
300
600
CNT Micro-Focus Field Emission X-Ray Source for in-vivo imaging of small animal cancer models
50-100um resolution, 0-50kVp, 1-3mA tube current, 10-100ms pulse width
CNT field emission imaging technologies Single source micro-CT Cyclops 1.0
Charybdis 1.0
J. Zhang et al (2005)
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
Respiratory gated μCT imaging (free-breathing anesthetized mice) (a)
(b)
(c)
(d)
Expiration
-12lp/mm at 10% MTF --50ms temporal resolution
peak (0.48ml)
Inspiration
base (0.53ml)
G. Cao et al. SPIE Medical Imaging 2008; G. Cao et al. Phys Med Biol 2009
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
Detection of Vascular Calcification Proximal aortic arch
CNT FE multi-pixel x-ray imaging Source Array
Stationary Tomosynthesis Micro-RT Single Cell Irradiation
Subject
IGRT Detector
[email protected]
Detector
Source Array
Stationary CT
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)
[email protected]
UNC Argus 2.0 : Stationary DBT Expected benefit: faster scanning time, better resolution, simpler design, lower imaging dose
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!
CT
Coronal Slice 1
Coronal Slice 2
NST
Region of better resolution
CNT-based irradiation technology development Update
CNT FE based x-ray pixel beam micro-RT (b) Micro-CT-RT
Prototype(a)micro-RT x
4.0cm
2D x-ray pixel beam array z
y
Multi-array system
[email protected]
Single array system
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
[email protected]
CNT micro-RT dosimetry (MC simulation)
2mm XPBA
1cm field
[email protected]
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: 150-200 um) Radiation SiO2 +Si
Assembled micro-RT.
Oncology
Physics & Astronomy
Image of prototype of multi-pixel micro-RT
[email protected]
Cathode chip design and fabrication 5x5
5 x 10 Electrical connection pads
CNT cathodes
[email protected]
Pixel beams are individually addressable 50 irradiation beams on
Electronic circuit Selected 10 irradiation beams on
[email protected]
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.
[email protected]
“NCI” irradiation pattern by electron and x-ray beams through individual controlling of cathodes
Electron pixel beams image
Energy: 30kV 2mm
Image from micro-RT x-rays measured by GAFCHROMIC film.
[email protected]
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.
Single pixel microbeam device
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL AAPM 2006 Orlando Chang (30)
SCI dose and dose rate calibration •
Dose is controlled by the number of emission current pulses;
•
Estimated dose rate range: cGy to 104 Gy per sec! FWHM = 28 μm
Dose rate: 103 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)
Cell irradiation demonstration (H2AX: DNA damage) (rat fibroblast cells)
Neg. control
23Gy, 30keV electron beam
pos. control
Multi-pixel Film Irradiation and Dosimetry
50 µm
FWHM: 40 um, dose: 29.1 Gy
1.45mm
Film Irradiation from 5x5 cathode array UNIVERSITY locations withOFallNORTH pixels CAROLINA AT CHAPEL HILL AAPM 2006 Orlando Chang (33) interconnected
SUMMARY z
Carbon nanotube field emission X-ray technology is capable of ultra-high temporal resolution imaging/irradiation and novel multi-pixel source array systems;
z
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;
z
Industry involvement is essential to realize the full potential of the technology (Xintek, Xinray, Siemens).
ACKNOWLEDGEMENTS Researcher team: Sigen Wang, Jerry Zhang, David Bordelon, Jared Snider, Eric Schreiber, Adrienne Cox, et al. • • • • • • • • •
NIH-U54-CA119343-01 (Cancer Nanotechnology Center of Excellence grant) NIH-NIBIB (4R33EB004204) NIH-NIBIB (4R33EB004204-03S1) NIH-NCI (R21 CA118351-01)* NIH (R21 CA128510-01)* North Carolina Biotechnology Center* UNC Lineberger Comprehensive Cancer Center Department of Homeland Security (TSWG) Xintek Inc. (UNC start-up company) *: Irradiation device grant
