New Advances in CT: Functional Imaging & Dose Reduction Ting-Yim Lee PhD, FCCPM; Xiaogang Chen PhD; Eugene Wong PhD; Nikolaj Jensen BSc; Glenn Bauman MD; Michael Lock MD; Barbara Fisher MD Lawson Health Research Institute; Robarts Research Institute; Medical Imaging, Physics & Astronomy and Oncology, The University of Western Ontario; London Regional Cancer Program London, Ontario, CANADA
Functional Imaging in Radiation Oncology • Target definition – Areas of increased invasiveness and resistance • Enhanced angiogenesis • Hypoxia – GTV, CTV • Monitoring of tumor response to treatment – Tumor mass – Reoxygenation – Shut down of vasculature – Adjuvant chemo and anti-angiogenesis therapy • Vascular normalization ** ** Jain. Science 307:58, 2005
Functional Imaging Modalities • Positron Emission Tomography (PET) • Single Photon Emission Tomography (SPECT) • Magnetic Resonance Imaging (MRI) • Computed Tomography ? – Anatomical/Morphological • Introduce CT Functional Imaging – Brain and liver tumor • Radiation dose from CT – Methods to reduce dose – In particular for CT functional imaging
CT Perfusion Brain Tumor Study CBF ml ⋅ min -1 ⋅ (100g) -1 200 0 CBV ml ⋅ (100g) -1 12 Deconvolution 0 MTT (s) 400 35 35 12 Tumor 350 Tumor 30 30 Artery 300 Vein Normal Normal 25 25 Brain Brain 250 20 20 200 HU HU HU Intravenous 0 15 15 150 Scan Protocol 10 10 Injection of 100 PS ml ⋅ min -1 ⋅ (100g) -1 5 5 50 20 Contrast Agent • 80 kVp, 190mA, 4 x 5 0 0 0 mm 0 0 40 40 80 80 120 120 160 160 40-50 ml @ 3- 0 40 80 120 160 -50 -5 -5 Time (s) Time (s) Time (s) 4 ml/s • 45 s cine scan 0 • 1 s every 16 s, 6 times
Basis of CT Perfusion (Functional) Imaging • Tissue curve is dependent on 200 Artery – Blood flow, blood volume, mean 150 transit time, capillary permeability 100 = ⋅ ∗ Q ( t ) F C ( t ) R ( t ) HU surface area product (PS) a 50 Q ( t ) : Tumor or brain curve – Arterial input concentration 0 C ( t ) : Arterial curve 0 40 80 120 160 • Tracer kinetics modeling a -50 F : Cerebral blood flow (CBF) Time (s) – Models tissue curve with above R(t) : Impulse Residue 35 parameters and arterial 30 Tumor Function (IRF) Fitted Curve concentration 25 ∗ : Convolutio n operator 20 • Fitting of measured tissue HU 15 curve with model curve 10 5 – Estimates of parameters 0 0 40 80 120 160 -5 Time (s)
Modeling of Tissue Contrast Kinetics • Johnson and Wilson Model * – Blood flow, transit time, transcapillary exchange, ven. outflow – Exchange regimes • Diffusion limited (F << PS); cold xenon • Flow limited (F>>PS); intravascular tracer: contrast agent in normal brain • Permeable (F ~ PS); contrast agent in most tissues, e.g. liver EES, C e (t), v e Blood Space, FC a (t) FC v (t) C b (x,t), v b PS x * Am J Physiol 210:1299-1303, 1966
CT Perfusion Imaging in Brain Tumors • Tissue Blood Flow (CBF, F) • Tissue Blood Volume (CBV, v b ) • Microvessel Permeability Surface Area (PS) • Mean transit time (MTT, T c ) = ⋅ ∗ Q ( t ) F C ( t ) R ( t ) T c a PS = - F ln(1-E) 1.0 k = FE/v e Q(t) (1-E) v b EES, R(t) C e (t), v e E Blood Space, FC a (t) C b (x,t), v b FC v (t) E·e -kt PS ≅ FE x Time Lee: Q J Nucl Med 41:171-87, 2003
Validation : Accuracy and Reproducibility • Rabbit VX2 brain tumor model • 13% and 7% for CBF and CBV CT vs. Microspheres CBF Measurements in Brain Tumours 250 Tumour Peri-Tumour Contra-lateral Normal 200 CT CBF (ml/min/100g) 150 100 m=0.97 r=0.86 50 0 RA 0 50 100 150 200 250 Microspheres CBF (ml/min/100g) Cenic & Lee: AJNR 21:462-470, 2000
Brain Tumor Studies • Primary brain tumor – glioma • Before and 1-2 weeks post radiation therapy • Changes in CT Perfusion functional parameters and response to treatment
Glioma-2
Glioma-2 • Blood flow map fused with planning CT • Whole brain irradiation • 50Gy/25
Glioma-2 Before MTT Blood Volume PS CECT Blood Flow After
Glioma-2 Before MTT Blood Volume PS CECT Blood Flow After
Glioma-2 Tumor Regions 150 ∗∗ P < 0.05 120 90 ∗∗ 60 ∗∗ 30 0 BF BV x 10 PS x 100 MTT X 10 (ml/min/100g) (ml/100g) (ml/min/100g) (s) Pre-Treatment Post-Treatment
Glioma-2 Normal Regions 60 ∗∗ P < 0.05 ∗∗ 45 30 ∗∗ 15 0 BF BV x 10 PS x 100 MTT X 10 (ml/min/100g) (ml/100g) (ml/min/100g) (s) Pre-Treatment Post-Treatment
Glioma-2 Jun 21 2006 Mar 23 2006 Sep 19 2006 Mar 07 2007
CT Liver Perfusion Study BF 250 200 Aorta Portal Vein 150 HU BV 100 50 Deconvolution 0 0 20 40 60 80 100 120 -50 MTT Time (s) Intravenous 250 [ ] Axial Shuttle 40 = ⋅ ⋅ + − ⋅ ∗ Injection of Q ( t ) F α C ( t ) ( 1 α ) C ( t ) R ( t ) 200 Aorta a p Portal Vein PS Contrast Agent 30 Q ( t ) : Tumor or liver curve 150 Hepatic Vein 20 HU HU C ( t ) : Aortic curve 100 a 10 C ( t ) : Portal venous curve 50 Tumor p Normal Liver 0 0 F : Total hepatic blood flow (BF) HAF 0 0 20 20 40 40 60 60 80 80 100 100 120 120 -50 -10 α : Hepatic arterial fraction (HAF) Hepatic Time (s) Time (s) Artery R(t) : Impulse Residue Function (IRF) PortaVein
CT Liver Perfusion Study • 8 x 5 mm thick slices for each • Couch ‘shuttles’ free location breathing patient between two locations • Total 80 mm coverage with 16 x 5 mm slices • Each location is scanned every 2.8 s • Images have to be sorted to reduce patient motion
CT Liver Perfusion Study Unsorted Sorted 300 300 250 250 Aorta Aorta Portal Vein Portal Vein 200 200 150 150 HU HU 100 100 50 50 0 0 0 20 40 60 80 100 120 0 20 40 60 80 100 120 -50 -50 Time (s) Time (s)
CT Liver Functional Maps Total Liver Blood Flow Hepatic Arterial Fraction (HAF) (ml ⋅ min -1 ⋅ (100g) -1 ) (% Total Blood Flow from Artery) • Metastasis was more hypovascular than surround normal liver tissue • Does it mean that the metastasis was hypoxic ?
CT Liver Functional Maps Total Blood Flow Hepatic Arterial Blood Flow (ml ⋅ min -1 ⋅ (100g) -1 ) HAF • Hepatic arterial blood flow (H A BF) in metastasis is greater than or equal to that in normal liver tissue • Metastasis might not be hypoxic, particularly in the rim • Indicates feasibility of radiation treatment for liver tumor?
Validation of CT Liver Perfusion • Seven New Zealand White Rabbits with implanted VX2 tumor in the liver Stewart & Lee. PMB 53:4249, 2008
CT Liver Perfusion Study • Objective – CT Perfusion functional parameters to distinguish tumor from normal tissue • 7 Hepatocellular Carcinoma (HCC), 5 metastases and 1 cholangioma • Each subject had a CT Perfusion Liver study with the free breathing axial shuttle technique • 120 kVp, 60 mAs, 0.4 s rotation period, 42 passes of the axial shuttle with the first 4 as baseline 300 injected at 3 ml ⋅ s -1 • 60 – 70 ml of Omnipaque at the 5 th pass of the axial shuttle
CT Liver Perfusion Study • Results – Total blood flow was lower while arterial blood flow was higher in the tumor than in normal tissue – Tumor may not be hypoxic Hepatic Arterial Fraction (%) Total Blood Flow Arterial Blood Flow (ml/min/100g) (ml/min/100g) 70 160 80 60 140 70 P < 0.05 P < 0.05 P < 0.05 120 50 60 100 50 40 80 40 30 60 30 20 40 20 10 20 10 0 0 0 Tumor Nomal Tumor Nomal Tumor Nomal
CT Radiation Dose • NCRP Report 160 – Ionizing Radiation Exposure of the Population of the US – 2006 • 414 million X-ray procedures – 62 million CTs (15%) • Collective radiation dose – 900,000 ** person-Sv (vs 124,000 in 1990) NEJM 357:2277, 2007 – 918,000 person-Sv from background – 440,000 person-Sv from CT From all ionizing radiation procedures including Nuclear Medicine and ** therapy
CT Radiation Dose • Typical effective dose of CT studies UK 2003 ** Europe 2004 ** Effective Effective CT Scan DLP DLP Dose Dose (mGy-cm) (mGy-cm) (mSv) (mSv) Routine Head 931 2.0 989 2.1 Abdomen (Liver metastases) 472 7.1 989 14.8 Chest, abdomen & pelvis (lymphoma staging or follow up 937 14.1 - - Chest (lung cancer: known, suspected or metastases) 575 8.1 430 6.0 ** Shrimpton et al. NRPB-W67, 2005 Effective DLP CT Functional Study Dose (mGy-cm) (mSv) Head (4 cm) 2289 4.8 Liver (axial shuttle – 8 cm) 1268 19.0
CT Dose Reduction – mA Modulation a) with patient size (adult vs c) according to patient thickness children) in the transaxial plane b) according to patient thick-ness d) Combination of a), b) and c) along longitudinal (z) axis e) Dose shield for helical scan MHRA Rep 05016, 2005, UK
CT Dose Reduction • mA modulation in the transaxial plane 34% ** • Dose reduction 22 – ** Greess et al. Eur Radiol 12:1571, 2002 Kalra et al. Radiology 233:649, 2004 Mastora et al. Eur Radiol 11:590, 2001
CT Dose Reduction • mA modulation along longitudinal (z) axis • Dose reduction by 32% on average ** Kalra et al. Radiology 233:649, 2004; ** 232:347, 2004
Recommend
More recommend
