中文摘要
核子醫學(SPECT、PET)在臨床前的小動物研究上佔有很重要的地位，利用設計過的偵檢器以及針孔準直儀，可以提高重建影像的解析度，以符合小動物造影需求。小動物SPECT依照中央視野(center field of view, CFOV)以及解析度的需求配備了多種規格的針孔準直儀，多規格的準直儀雖然可以讓儀器得到很好的發揮，但是也使得成本門檻提高。另一方面，近幾年來SPECT/PET雙模態同時造影技術正在積極的發展當中，其原理是利用SPECT/PET兩種核種同位素同時進行掃描，我們稱之為雙同位素同時掃描(dual isotope simultaneous acquisition, DISA)。雙同位素同時掃描在臨床前研究以及臨床應用上有著很大的優勢，此項技術可以同時取得兩種互補的功能性分子影像，增加影像比對參考的價值以及消除分次掃描的誤差可能性。但是雙同位素同時掃描會產生能譜交疊(cross-talk)散射汙染，影響影像品質，所以必須進行散射校正移除散射。本研究發展了一套射束擋塊(beam stopper, BS) SPECT成像方法，並且可將射束擋塊裝置應用在PET掃描儀中達到SPECT/PET雙模態造影進行雙同位素掃描，該裝置更具有能夠避免能譜交疊散射汙染的特性。
射束擋塊可以被視為針孔準直儀的相反材質，其利用高衰減材質取代針孔準直儀的針孔部分，並將其他針孔準直儀高衰減材質的部分移除，所以利用射束擋塊所得到的投影分布與針孔準直儀的投影分布相反。而射束擋塊成像程序上即是利用有無射束擋塊的兩次掃描分布相減，來得到與針孔準直儀掃描相似的投影分布。射束擋塊裝置由4根直徑0.8 mm的棍狀射束擋塊與41片厚度為0.5 mm的隔板(septa)所組成，本研究將射束擋塊置入Inveon PET進行掃描，透過旋轉射束擋塊裝置可以得到全角度的有無射束擋塊掃描投影分布，再將投影數據相減即可得到全角度的射束擋塊SPECT重建投影資訊，另一方面射束擋塊裝置並不會干擾PET掃描，因此可達到雙同位素同時性掃描的效果。
本研究使用蒙地卡羅模擬驗證該方法的可行性，實驗分為兩階段實施，第一階段我們先驗證射束擋塊SPECT成像性能的評估，第二階段再將該BS裝置置於PET儀器中評估應用BS進行雙模態掃描的可行性。
在射束擋塊SPECT性能評估實驗中得到系統空間解析度約為1.2 mm，變異係數(均勻性評估)為6.49%，對比還原係數(對比還原評估)可達94.90%，體積靈敏度為152.85 cps/MBq∙cm2。在SPECT/PET雙模態掃描的實驗中，應用BS裝置進行SPECT/PET雙模態造影可有效去除能譜交疊的散射汙染，值得注意的是SPECT/PET雙模態掃描可保持幾乎與單模態個別掃描相同的影像品質。
本研究提出了射束擋塊裝置在小動物造影設備上的應用，其在小動物SPECT擁有節省裝置成本，增加操作靈活性的特色。並且應用在PET儀器上進行SPECT/PET雙模態同時性造影可以避免高能光子的能譜交疊散射汙染達到良好的影像品質。

Abstract
Nuclear medicine image can achieve the ultra-high resolution level through the design of detector and pinhole collimator. According to desired resolution and center field of view (CFOV), micro-SPECT is supplied with a lot of specification of collimators. Although adequate collimator allows micro-SPECT fully demonstrated its performance, it often needs high cost. On the other hand, dual tracer imaging with SPECT/PET imaging has active developed in recent years. The procedure is to inject dual tracer (ex: 99mTc and 18F) in body and perform SPECT and PET imaging simultaneously. The process is called “Dual Isotope Simultaneous Acquisition, DISA”. DISA has great advantage in both pre-clinical and clinical applications, it can evaluate the functional imaging of different tracers under identical condition, increase physiological assessment accuracy and reduce errors of separate scans. However, DISA would produce cross-talk scatter contamination to degrade the image quality. As a result, a robust cross-talk scatter correction is essential for classical DISA imaging with SPECT/PET. This study propose a novel Beam Stopper (BS) imaging technique based on PET scanner that enables SPECT/PET dual modality imaging. Instead of the insert of pinhole collimator inside SPECT, the BS insert inside PET scanner can achieve SPECT and PET imaging without the contamination of cross-talk scatter.
BS device can be regarded as the opposite of pinhole collimator system, it uses high attenuated material to replace the part of pinhole aperture and remove the other part of pinhole collimator. Using the difference between complete projection data (scan w/o BS) and the BS-scanning projection data, we can obtain a projection data similar to the pinhole imaging. This BS device consisted of four tungsten BS rod with 0.8 mm diameter and forty one discs septa with 0.5-mm-thickness. BS device inserted into Inveon preclinical PET system can acquired full SPECT projection data sets via rotations of BS device, while obtaining PET images with normal PET acquisitions.
The feasibility of the study is validated with extensive Monte Carlo simulations. The experiment is divided into two steps. In the first step, we evaluate the performance of BS-SPECT system. Next, we put the BS device inside Inveon preclinical PET to assess the feasibility of dual tracer imaging using BS technique. For BS-SPECT studies, high resolution (~1.2mm), uniformity (CV=6.49%) and 152.85 cps/Bq∙cm2 of volume sensitivity were obtained. For contrast phantom studies, CRC in hot area and cold area can achieve 94.90% and 90.35%, respectively. For DISA studies, the cross-talk scatters can be removed naturally during the subtraction of the sinograms with and w/o BS. SPECT/PET dual modality imaging can maintain the same image quality compared with single modality scan.
This study has proposed a novel beam stopper imaging technique that opens the new way for high resolution molecular imaging. Comparing to other micro SPECT, BS has the advantages of low cost and more flexibility and enable the SPECT/PET dual modality imaging while eliminating the cross-talk scatter contaminations.

參考文獻
Abbey C K, Borowsky A D, McGoldrick E T, Gregg J P, Maglione J E,
Cardiff R D and Cherry S R 2004 In vivo positron-emission tomography
imaging of progression and transformation in a mouse model of
mammary neoplasia Proceedings of the National Academy of Sciences of
the United States of America 101 11438-43

Bartoli A, Belcari N, Del Guerra A and Fabbri S Nuclear Science
Symposium Conference Record, 2007. NSS'07. IEEE,2007), vol. Series
5): IEEE) pp 3408-13

Beekman F J, van der Have F, Vastenhouw B, van der Linden A J, van
Rijk P P, Burbach J P and Smidt M P 2005 U-SPECT-I: a novel system
for submillimeter-resolution tomography with radiolabeled molecules in
mice Journal of nuclear medicine : official publication, Society of
Nuclear Medicine 46 1194-200

Boisson F, Zahra D, Parmar A, Gregoire M C, Meikle S R, Hamse H and
Reilhac A 2013 Imaging capabilities of the Inveon SPECT system using
single-and multipinhole collimators Journal of nuclear medicine : official
publication, Society of Nuclear Medicine 54 1833-40

Chapman S E, Diener J M, Sasser T A, Correcher C, Gonzalez A J,
Avermaete T V and Leevy W M 2012 Dual tracer imaging of SPECT and
PET probes in living mice using a sequential protocol American journal
of nuclear medicine and molecular imaging 2 405-14

Cherry S R, Sorenson J A and Phelps M E 2012 Physics in nuclear
medicine: Elsevier Health Sciences)

Dahlbom M, MacDonald L, Schmand M, Eriksson L, Andreaco M and
Williams C 1998 A YSO/LSO phoswich array detector for single and
coincidence photon imaging Nuclear Science, IEEE Transactions on 45
1128-32

DeBenedetti S, Cowan C, Konneker W and Primakoff H 1950 On the
angular distribution of two-photon annihilation radiation Physical Review
77 205

Del Guerra A, Damiani C, Di Domenico G, Motta A, Giganti M,
Marchesini R, Piffanelli A, Sabba N, Sartori L and Zavattini G 2000 An
integrated PET-SPECT small animal imager: preliminary results Nuclear
Science, IEEE Transactions on 47 1537-40

Deprez K, Van Holen R and Vandenberghe S 2014 A high resolution
SPECT detector based on thin continuous LYSO Physics in medicine and
biology 59 153-71

Dewaraja Y, Li J and Koral K 1998 Quantitative 131 I SPECT with triple
energy window Compton scatter correction Nuclear Science, IEEE
Transactions on 45 3109-14

El Fakhri G, Mahmood A and Ouyang J 2006 Quantitative
simultaneous dual isotope micro-SPECT in the small animal. Journal of
nuclear medicine : official publication, Society of Nuclear Medicine

Fessler J 2012 Image reconstruction toolbox Available at website:
http://www. eecs. umich. edu/fessler/code

Furenlid L R, Wilson D W, Chen Y C, Kim H, Pietraski P J, Crawford M
J and Barrett H H 2004 FastSPECT II: A Second-Generation
High-Resolution Dynamic SPECT Imager IEEE transactions on nuclear
science 51 631-5

Goorden M C, van der Have F, Kreuger R, Ramakers R M, Vastenhouw
B, Burbach J P, Booij J, Molthoff C F and Beekman F J 2013 VECTor: a
preclinical imaging system for simultaneous submillimeter SPECT and
PET Journal of nuclear medicine : official publication, Society of
Nuclear Medicine 54 306-12

Guerra P, Rubio J L, Ortuno J E, Kontaxakis G, Ledesma M J and Santos
A 2007 Performance analysis of a low-cost small animal PET/SPECT
scanner Nuclear Instruments and Methods in Physics Research Section A:
Accelerators, Spectrometers, Detectors and Associated Equipment 571
98-101
Ichihara T, Ogawa K, Motomura N, Kubo A and Hashimoto S 1993
Compton scatter compensation using the triple-energy window method
for single- and dual-isotope SPECT Journal of nuclear medicine : official
publication, Society of Nuclear Medicine 34 2216-21

Ishizu K, Mukai T, Yonekura Y, Pagani M, Fujita T, Magata Y, Nishizawa
S, Tamaki N, Shibasaki H and Konishi J 1995 Ultra-high resolution
SPECT system using four pinhole collimators for small animal studies
Journal of nuclear medicine : official publication, Society of Nuclear
Medicine 36 2282-7

Jaszczak R J, Li J, Wang H, Zalutsky M R and Coleman R E 1994
Pinhole collimation for ultra-high-resolution, small-field-of-view SPECT
Physics in medicine and biology 39 425-37

Jeavons A, Chandler R and Dettmar C 1999 A 3D HIDAC-PET camera
with sub-millimetre resolution for imaging small animals Nuclear
Science,IEEE Transactions on 46 468-73

Kastis G A, Furenlid L R, Wilson D W, Peterson T E, Barber H B and
Barrett H H 2004 Compact CT/SPECT small-animal imaging system
Nuclear Science, IEEE Transactions on 51 63-7

Levin C S and Hoffman E J 1999 Calculation of positron range and its
effect on the fundamental limit of positron emission tomography system
spatial resolution Physics in medicine and biology 44 781-99

Liu Z, Kastis G A, Stevenson G D, Barrett H H, Furenlid L R, Kupinski
M A, Patton D D and Wilson D W 2002 Quantitative analysis of acute
myocardial infarct in rat hearts with ischemia-reperfusion using a
high-resolution stationary SPECT system Journal of nuclear medicine :
official publication, Society of Nuclear Medicine 43 933-9

Maglione J E, Moghanaki D, Young L J, Manner C K, Ellies L G, Joseph
S O, Nicholson B, Cardiff R D and MacLeod C L 2001 Transgenic
Polyoma middle-T mice model premalignant mammary disease Cancer
research 61 8298-305

Magota K, Kubo N, Kuge Y, Nishijima K, Zhao S and Tamaki N 2011
Performance characterization of the Inveon preclinical small-animal
PET/SPECT/CT system for multimodality imaging European journal of
nuclear medicine and molecular imaging 38 742-52

Malakoff D 2000 The rise of the mouse, biomedicine's model mammal
Science 288 248-53

Metzler S D, Jaszczak R J, Patil N H, Vemulapalli S, Akabani G and Chin
B B 2005 Molecular imaging of small animals with a triple-head SPECT
system using pinhole collimation IEEE transactions on medical imaging
24 853-62

Miyaoka R S, Janes M L, Lee K, Park B, Kinahan P E and Lewellen T K
2005 Development of a single detector ring micro crystal element
scanner: QuickPET II Molecular imaging 4 117-27

Pichler B J, Gremillion T, Ermer V, Schmand M, Bendriem B, Schwaiger
M, Ziegler S I, Nutt R and Miller S D 2003 Detector characterization and
detector setup of a NaI-LSO PET/SPECT camera Nuclear Science, IEEE
Transactions on 50 1420-7

Rouze N C, Schmand M, Siegel S and Hutchins G D 2004 Design of a
small animal PET imaging system with 1 microliter volume resolution
Nuclear Science, IEEE Transactions on 51 757-63

Rowland D J and Cherry S R 2008 Small-animal preclinical nuclear
medicine instrumentation and methodology Seminars in nuclear medicine
38 209-22

Saoudi A and Lecomte R 1999 A novel APD-based detector module for
multi-modality PET/SPECT/CT scanners Nuclear Science, IEEE
Transactions on 46 479-84

Schramm N, Hoppin J, Lackas C, Gershman B, Norenberg J and de Jong
M Society of Nuclear Medicine Annual Meeting Abstracts,2007), vol.
Series 48): Soc Nuclear Med) p 436P

Schramm N, Lackas C, Hoppin J, Schurrat T, Béhé M, Engeland U and
Behr T Nuclear Science Symposium Conference Record, 2004
IEEE,2004), vol. Series 5): IEEE) pp 2823-4

Soret M, Bacharach S L and Buvat I 2007 Partial-volume effect in PET
tumor imaging Journal of nuclear medicine : official publication, Society
of Nuclear Medicine 48 932-45

Stickel J R and Cherry S R 2005 High-resolution PET detector design:
modelling components of intrinsic spatial resolution Physics in medicine
and biology 50 179-95

Sychra J and Blend M 1996 A method for simultaneous dual energy
SPECT imaging of prostate cancer. J. Nuclear Medicine

Tai Y C, Chatziioannou A F, Yang Y, Silverman R W, Meadors K, Siegel
S, Newport D F, Stickel J R and Cherry S R 2003 MicroPET II: design,
development and initial performance of an improved microPET scanner
for small-animal imaging Physics in medicine and biology 48 1519-37

Tai Y C, Ruangma A, Rowland D, Siegel S, Newport D F, Chow P L and
Laforest R 2005 Performance evaluation of the microPET focus: a
third-generation microPET scanner dedicated to animal imaging Journal
of nuclear medicine : official publication, Society of Nuclear Medicine 46
455-63

Tai Y C, Wu H, Pal D and O'Sullivan J A 2008 Virtual-pinhole PET
Journal of nuclear medicine : official publication, Society of Nuclear
Medicine 49 471-9

Vaissier P E, Goorden M C, Vastenhouw B, van der Have F, Ramakers R
M and Beekman F J 2012 Fast spiral SPECT with stationary
gamma-cameras and focusing pinholes Journal of nuclear medicine :
official publication, Society of Nuclear Medicine 53 1292-9

van der Have F, Vastenhouw B, Ramakers R M, Branderhorst W, Krah J
O, Ji C, Staelens S G and Beekman F J 2009 U-SPECT-II: An
Ultra-High-Resolution Device for Molecular Small-Animal Imaging
Journal of nuclear medicine : official publication, Society of Nuclear
Medicine 50 599-605

Vanhove C, Defrise M, Lahoutte T and Bossuyt A 2008 Three-pinhole
collimator to improve axial spatial resolution and sensitivity in pinhole
SPECT European journal of nuclear medicine and molecular imaging 35
407-15

Wagenaar D, Zhang J, Kazules T, Vandehei T, Bolle E, Chowdhury S,
Parnham K and Patt B Nuclear Science Symposium Conference Record,
2006. IEEE,2006), vol. Series 6): IEEE) pp 3821-6

Yang Y, Tai Y C, Siegel S, Newport D F, Bai B, Li Q, Leahy R M and
Cherry S R 2004 Optimization and performance evaluation of the
microPET II scanner for in vivo small-animal imaging Physics in
medicine and biology 49 2527-45

Yao R, Deng X, Beaudoin J-F, Ma T, Cadorette J, Cao Z and Lecomte R
2013 Initial evaluation of LabPET/SPECT dual modality animal imaging
system IEEE transactions on nuclear science 60 76-81

沈承緯 2013 Optimizing the system parameters of BS-SPECT for small
animals imaging