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Perfusion CT of head and neck cancer
European Journal of Radiology 83 (2014) 537–544
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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Review
Perfusion CT of head and neck cancer夽 Ahmed Abdel Khalek Abdel Razek ∗ , Ahmed Mohamed Tawfik, Lamiaa Galal Ali Elsorogy, Nermin Yehia Soliman Diagnostic Radiology Department, Mansoura Faculty of Medicine, Mansoura 13551, Egypt
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Article history: Received 12 September 2013 Received in revised form 5 December 2013 Accepted 8 December 2013 Keywords: Perfusion CT Head and neck Squamous cell carcinoma Recurrence
a b s t r a c t We aim to review the technique and clinical applications of perfusion CT (PCT) of head and neck cancer. The clinical value of PCT in the head and neck includes detection of head and neck squamous cell carcinoma (HNSCC) as it allows differentiation of HNSCC from normal muscles, demarcation of tumor boundaries and tumor local extension, evaluation of metastatic cervical lymph nodes as well as determination of the viable tumor portions as target for imaging-guided biopsy. PCT has been used for prediction of treatment outcome, differentiation between post-therapeutic changes and tumor recurrence as well as monitoring patient after radiotherapy and/or chemotherapy. PCT has a role in cervical lymphoma as it may help in detection of response to chemotherapy and early diagnosis of relapsing tumors. © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Head and neck cancer accounts for up to 5–10% of all cancers. The most common pathologic type (90%) is squamous cell carcinoma. The diagnostic work-up of head and neck cancer relies on CT and MRI, and the main clinical value is staging the disease by accurately determining tumor volume, assessing its extension and detection of lymph node metastases. Conventional CT and MRI, however, provide mainly anatomic information and rely on morphologic changes with very little information about tumor physiology or functional behavior [1–3]. Functional MR imaging modalities such as diffusion MR imaging, dynamic susceptibility perfusion contrast MR imaging and MR spectroscopy [4–6] as well as positron-emission tomography (PET) have been applied to investigate head and neck cancer [7]. PCT has been used to obtain measures of tumor vascular physiology and hemodynamics. The basic principle of PCT is recording time changes in X-ray attenuation over a fixed area of interest during passage of a fast bolus of iodinated contrast medium through the region. The dynamic acquisitions cover the first pass of
Abbreviations: BF, blood flow; BV, blood volume; CM, contrast medium; EGFR, epidermal growth factor receptor; MTT, mean transit time; MVD, microvessel density; HNSCC, head and neck squamous cell carcinoma; PCT, perfusion CT; ROI, region of interest; PS, permeability surface area product; TAC, time attenuation curve; SCC, squamous cell carcinoma; VEGFR, vascular endothelial growth factor. 夽 Presented as educational exhibit at American Society of Neuroradiology (ASNR) 2012. ∗ Corresponding author. Tel.: +20 161948567; fax: +20 502315105. E-mail addresses: [email protected] (A.A.K.A. Razek), ahm m tawfi[email protected] (A.M. Tawfik), [email protected] (L.G.A. Elsorogy), nermin [email protected] (N.Y. Soliman). 0720-048X/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejrad.2013.12.008
iodinated contrast medium in the regional vascular bed, during which it has an intravascular distribution. Mathematical analysis of data obtained from PCT allows an objective measurement of tissue perfusion imaging biomarkers [8–11]. Several studies have discussed the potential applications of PCT in oncology in different regions of the body [9–11], as well as in head and neck tumors [12–14]. Tumor angiogenesis is the process of development of new capillary beds in tumors and is necessary for tumor growth and metastatic spread [11,12]. Tumors cannot grow beyond 0.1–0.2 mm in size without the induction of angiogenesis. Angiogenesis plays an important role in HNSCC. Histopathologic evaluation of biomarkers of angiogenesis such as microvessel density (MVD) and epidermal growth factor receptor (EGFR) is expensive, invasive and not widely practiced techniques [8–12]. The principles for computation of perfusion parameters for MR and CT are similar. However, there are several differences in technique. The most important advantage of PCT is the linear relationship between contrast concentration and attenuation in CT, which facilitates quantitative (versus relative) measurement of BF and BV. This is in contrast to the non-linear (logarithmic) relation between signal intensity and concentration of paramagnetic contrast medium in MR perfusion. MR perfusion is also limited by its poor reproducibility caused by differences in pulse sequences and MRI hardware as well as its greater susceptibility to image artifacts caused by metal or air–bone interfaces. Other advantages of PCT include higher spatial resolution and its relative availability. The disadvantages of PCT compared to MRI include the relatively limited coverage of PCT, the use of ionizing radiation and iodinated contrast medium [10–13]. Compared to PET, PCT is more available and less expensive. PET has the advantage of whole body imaging, but represents an
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Table 1 Protocol for perfusion CT of head and neck. Non enhanced CT acquisition Coverage area: at 64 detector scanner 40 mm Dynamic CT acquisition Acquisition mode: cine mode Tube rotation time: 1 ms Acquisition parameters Tube voltage: 80 kVp for lower radiation dose Tube current: 100 mA s Slice thickness: 5 mm, 8 sections Contrast medium Method: automatic injector Volume: 40 ml Rate of injection: 6 ml/s Start of scan: 6 s after start of contrast injection End of scan: duration 55 s ROI of arterial input Site: at ICA Arterial time attenuation curve Method: automatic
extra-step in the management of HNSCC patients and is not without limitations. The role of PET in investigation of primary neck tumors or detection of metastatic lymph nodes is still not well established and until now PET is not recommended in most guidelines for routine diagnosis and staging of head and neck cancer [7]. However, PET may have an important role in monitoring treatment response and detection of recurrence. In this article, we review technique and clinical applications of PCT in head and neck cancer.
ratio decreases by only 11% [8,9]. The tube current should also be lowered as possible, either with fixed tube current settings or with automated tube current modulation techniques, which allow more homogeneous distribution of noise. Choice of slice thickness varied from 2.5 to 5 mm, depending on the scanned region. Thicker sections decrease image noise but on the expense of lower spatial resolution [13,14]. The sampling rate or temporal resolution varies according to the analytic method used. Deconvolution-based analysis requires a higher temporal resolution than studies using compartmental based analysis. Most studies on head and neck PCT were done using deconvolution-based methods and the recommended temporal resolution has been 1 image every second. A higher the temporal resolution means a greater number of data points, but it increases the radiation exposure and limits the scan range [9–13]. 2.1.4. Contrast medium administration Contrast medium (CM) with high iodine concentration (370–400 mg/L) is preferable because it produces greater tissue enhancement. The volume of contrast bolus varies between studies from 40 to 70 ml, but usually a volume of 40 ml is used. Injection rates ranging between 3.5 and 10 ml/s are typically adequate for PCT. Compartmental analytic methods require higher injection rates while deconvolution-based methods permit lower rates. To keep the contrast bolus compact, a subsequent saline flush of 20–40 ml at the same flow rate is recommended. The scan delay for cine acquisition from the start of CM injection is determined by the CM circulation time to the region of interest. Typically, a scan delay of 5–10 s is suitable [9–11].
2. Techniques
2.2. Post-processing
Perfusion CT protocol consists of a baseline unenhanced acquisition, followed by a dynamic acquisition performed during intravenous injection of contrast medium [8–10]. Table 1 shows protocol for PCT of head and neck.
2.2.1. Arterial input selection Many studies have addressed the choice of arterial input, which is an essential step for PCT calculation [15,16]. The selected artery must be perpendicular to the imaging plane and large enough to minimize partial volume effects. In PCT of the head and neck region, the choice of either the internal or external carotid has no significant effect on PCT calculations [17]. The internal carotid artery is used as the arterial input because of its better visualization, perpendicular course, and larger caliber, all of which decrease partial volume effects. It is recommended to use the artery ipsilateral to the tumor, but the use of contralateral artery is justified in case of severe tumor encasement of the ipsilateral artery. The arterial region of interest (ROI) should be inserted in a section proximal to any visible arterial plaques to avoid any errors [16,17].
2.1. Data acquisition 2.1.1. Unenhanced CT acquisition The baseline unenhanced CT acquisition serves as a localizer to select the appropriate tissue area to be included in the contrastenhanced dynamic imaging range, therefore a lower dose, thicker section scanning should be used [12]. 2.1.2. Dynamic CT acquisition The first-pass study for PCT comprises images acquired in a cine-mode (axial acquisition with continuous tube rotation without table motion) for a total of 40–60 s. For permeability measurements, a second phase is obtained after 2–10 min [12,13]. 2.1.3. Acquisition parameters Depending on the scanner configuration, a 2-cm scan range (16row CT scanner), a 4-cm scan range (64-row CT scanner) or 8–16 cm (128- or 320-row CT detector) can be selected for dynamic scanning. Selection of acquisition parameters for PCT varies according to the scanned region, the configuration of the scanner and the mathematical analysis technique used. The balance between radiation exposure, image noise, spatial and temporal resolutions is of utmost importance. To reduce radiation exposure, it is advisable to use a low tube voltage (80–100 kVp) protocol. The increase in image noise is counterbalanced by an increase in attenuation of iodine at low tube voltage, so that the signal to noise ratio is kept constant or slightly decreases [12,13]. Perfusion CT at 80 kVp decreases the radiation dose up to 300% compared to 120 kVp, while the signal to noise
2.2.2. Arterial time attenuation curve (TAC) An arterial TAC is generated after selection of the arterial ROI. The curve should contain a first-pass phase with steep rise and high peak followed by steep decay and then a small peak representing recirculation (Fig. 1). The end of first pass is defined as the lowest point reached after maximal peak and before recirculation peak. Some software packages can identify the end of first pass automatically; but the automatic identification may lead to inaccuracies and manual identification is recommended. Early or late selection of the end of first pass is associated with substantial changes in perfusion parameters [10,16]. 2.2.3. Tumor region of interest (ROI) A ROI must be inserted inside the tumor so that the software may quantify perfusion values within it. In placing the ROI, special attention should be paid to ensuring that it does not include large vessels, air or surrounding adipose tissue. It is vital that the ROI remains confined within the tumor margins in the whole dynamic perfusion series, and any subtle patient’s motion during the scan
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2.4.1. Blood flow (BF) map BF map is defined as flow rate of blood through the vasculature in tissue region. It is measured in ml/min/100 g of tissue. BF includes flow in large vessels, arterioles, capillaries, venules and veins as well as arteriovenous shunts. It represents tumor vascularity and grade. It is the most reliable parameter for differentiation of malignant from benign tumors [8,9]. 2.4.2. Blood volume (BV) map BV map is defined as the volume of blood within vasculature in a tissue region that flows. It is measured in ml/100 g of tissue. The BV includes blood in large vessels, arterioles, capillaries, venules and veins. It represents tumor vascularity [9,10]. 2.4.3. Mean transit time (MTT) map MTT map is defined as average time taken by blood elements to traverse the vasculature from the arterial end to the venous end. It is expressed in seconds. It is thought as a surrogate marker for perfusion pressure [8,9]. Fig. 1. Arterial time attenuation curve (TAC). TAC represents attenuation in the arterial input plotted against time. The first pass of contrast medium appears in the left part of curve with steep up-slope, high peak enhancement, and quick decay; and is followed by recirculation phase.
which changes the position of the ROI will cause errors in calculation. The use of manually drawn free-hand ROI traced around tumor margins is preferred to circular or oval software based ROIs because tumor perfusion is spatially heterogeneous [9,12]. The tumor ROI may be inserted in only a single section showing the maximal tumor dimensions, or alternatively in multiple sections and then average values taken. No significant differences were observed between the 2 methods in PCT of HNSCC [18]. 2.3. Analysis of perfusion CT 2.3.1. Deconvolution analysis When a contrast bolus arrives in an artery supplying a given region of the body, it undergoes delay and dispersion. Deconvolution attempts to correct for this effect. Deconvolution of the arterial input function and tissue curves can be accomplished using a variety of techniques. Singular value decomposition has yielded the most robust results from all the deconvolution methods and has gained widespread acceptance [8,9]. 2.3.2. Compartmental analysis In kinetic modeling technique, analysis can be undertaken using the single compartment or double-compartment method. The single compartmental method assumes that the intravascular and extravascular spaces are a single compartment and calculates tissue perfusion based on the conservation of mass within the system (i.e., using Fick’s principle). It estimates perfusion using the maximal slope or the peak height of the tissue concentration curve normalized to the arterial input function. Conversely, the double-compartmental method assumes that intravascular and extravascular spaces are separate compartments and estimates capillary permeability and BV using Patlak analysis, which quantifies the passage of contrast from the intravascular space into the extravascular space [10,11]. 2.4. Parametric perfusion maps Compartmental based software produces perfusion maps (BF, BV and MTT). While deconvolution based software can also generate PS map [12] (Fig. 3).
2.4.4. Permeability surface area product (PS) PS is product of permeability and the total surface area of capillary endothelium in a unit mass of tissue (usually 100 g of tissue). It is expressed in ml/min/100 g. Measurement of PS is a surrogate marker for immature leaky vessels [10,11]. 3. Clinical applications 3.1. Head and neck squamous cell carcinoma 3.1.1. Differentiation of HNSCC from normal muscles HNSCC demonstrates increased CP, BF, BV, and decreased MTT compared with normal tissue or benign lesions. Many studies on PCT of HNSCC demonstrated significant increase in BF, BV, and PS together with significant reduction in MTT in HNSCC as compared to adjacent normal muscle [19–21] (Fig. 2). 3.1.2. Extension of HNSCC CTP can differentiate HNSCC from adjacent normal muscles. This difference can aid in delineation of the outlines of the tumor from adjacent soft tissue. Also, it helps to detect extensions of the tumor and infiltration of the surrounding soft tissue. Accurate detection of tumor extension in the head and neck is important for tumor staging [22,23] (Fig. 3). 3.1.3. Metastatic cervical lymph nodes Presence of metastatic lymph nodes in patients with HNSCC changes the tumor stage, treatment strategy and significantly worsens the prognosis [24,25]. Characterization of cervical lymph nodes in patients with HNSCC is difficult by cross-sectional anatomic and functional MR imaging. In one study, metastatic lymph nodes (Fig. 4) had higher perfusion than benign nodes, although the difference was not significant [26]. In another study, BF, BV and PS were significantly higher for metastatic nodes in hypopharyngeal and laryngeal carcinoma compared to benign cervical lymph nodes [27]. 3.1.4. Guidance for biopsy PCT maps can differentiate viable from necrotic regions of HNSCC and other malignant tumors of head and neck. The viable regions of malignancy show high BF and BV, while the necrotic regions display low BF and BV. This has the potential for guiding biopsy to the region with highest BF and BV on PCT maps, thus can help in reducing sampling errors [28].
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Fig. 2. Retromolar trigone squamous cell carcinoma. (a) Contrast CT image shows a region of interest drawn within the tumor in the right retromolar trigone. The tumor cannot be well delineated from surrounding soft tissue. (b) BF map shows high BF of the tumor as demonstrated by light blue and green colors; compared to the surrounding muscles with darker blue colors. Quantitative BF of the tumor is 86.6 ml/min/100 g compared to 12.1 ml/min/100 g in the muscles.
3.1.5. Biomarker of angiogenesis It was found that increased blood flow on PCT is correlated with angiogenesis and increased tumor vascularity, and increased tumor vascularity is associated with local recurrence and metastasis [29–31]. The BF and BV of HNSCC correlated positively with MVD, indicating the potential of PCT for assessing angiogenesis [29]. A significant correlation was detected between PCT measures and epidermal growth factor receptor (EGFR) overexpression in HNSCC, suggesting that PCT may be used for monitoring molecular biomarkers. EGFR is considered a risk factor for recurrence and disease-specific death in HNSCC [30]. In another study, there was a significant positive correlation between relative blood flow, measured by PCT and interleukin-8 level in patients with HNSCC. Because interleukin-8 is a biomarker of increased angiogenesis, PCT may be used in HNSCC patients for prediction of increased angiogenesis and tumor aggressiveness and selection of patients who may benefit from treatment with antiangiogenic drugs [31]. 3.1.6. Prediction of response to radio- and chemotherapy Few studies discussed the prediction of response of HNSCC to radio and chemotherapy with PCT [32–36]. Low perfusion of HNSCC is associated with higher rates of local failure of radiation therapy [34]. PCT may be able to identify patients who will successfully respond to induction chemotherapy, which could potentially
Fig. 3. Left supraglottic squamous cell carcinoma. (a) Contrast CT image showing a region of interest drawn within the tumor in the left aryepiglottic fold. (b) BV map shows high BV of the tumor as demonstrated by green, yellow and red colors; compared to the surrounding muscles with blue colors. Quantitative BV of the tumor is 5.4 ml/100 g compared to 1.1 ml/100 g in the muscles.
eliminate this step for subsequent patients when deciding on the appropriate treatment regimen [35]. PCT parameters can be regarded as an independent predictor of local failure in irradiated HNSCC. In a previous study, the pretreatment tumor BF and capillary permeability were significantly higher in patients who achieved locoregional control than those with treatment failure [36]. 3.1.7. Differentiation of recurrence from post therapeutic changes Post-therapeutic changes are difficult to differentiate from tumor recurrence on conventional CT or MRI, because they show a similar degree of enhancement [37]. In a study on SCC of the oral cavity and oropharynx after chemo-radiation treatment, there was no statistical difference in perfusion parameters between primary and recurrent tumors. Recurrent disease could be differentiated on
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Fig. 4. Metastatic cervical lymph node. (A) Contrast CT scan shows enlarged metastatic lymph node infiltrating left sternocleidomastoid muscle. (B) BV map shows high perfusion in the metastatic left cervical lymph node as compared to healthy contralateral muscle. BV of metastatic node is 5.5 ml/100 g compared to 1.3 ml/100 g in muscle.
the basis of significantly higher BF from post-therapeutic changes [38]. In another study on nasopharyngeal carcinoma treated with radiotherapy, recurrent tumors had significantly higher BF, BV and PS than post-radiation changes [39] (Fig. 5). 3.1.8. Monitoring of HNSCC after therapy The gold standard for monitoring of HNSCC after therapy is endoscopy and biopsy. Variable degrees of decrease in BV, BF and PS are observed in responders after induction chemotherapy. A statistically significant correlation was found between 20% reduction of BV at CTP and 50% reduction of tumor volume at endoscopy after chemotherapy [40]. Another study reported that after chemotherapy BF and BV significantly decreased and the MTT significantly increased in the responders group. The decrease in BF and BV correlated with tumor volume reduction after chemotherapy. No such changes are observed in non-responders [41]. The serial changes of PCT parameter after chemoradiotherapy were monitored in another study. In the responders, the perfusion parameter values
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Fig. 5. Recurrence at the right cheek after excision and radiotherapy of right maxillary carcinoma. (A) CT scan shows heterogeneous enhancement of the right maxillary sinus and surrounding tissue. (B) BF map shows high BF (84 ml/min/100 g) of the soft tissue of the right check denoting recurrence compared to low BF (13 ml/min/100 g) of the lesion in the right maxillary sinus denoting non-neoplastic inflammatory tissue.
over the course of treatment showed either a pattern of significant constant reduction (BF), of significant initial reduction followed by a plateau (BV), or non-significant fluctuations (MTT and PS). Nonresponders demonstrated an acute increase of BF, BV, and PS [42]. Also, there is correlation between CTP parameters and standardized uptake values in treatment response [43]. 3.2. Lymphoma Both Hodgkin’s disease (HD) and non-Hodgkin’s lymphoma (NHL) frequently occur in the head and neck. Marked elevation of BF, BV and PS and reduction of MTT were observed in primary sphenoid sinus lymphoma (Fig. 6) [44]. In another study, higher perfusion was observed in active lymphoma compared to inactive lymphoma. Progression of disease on serial evaluation from inactive to active was also associated with increase in perfusion [45]. Untreated lymphoma has higher BF, BV and PS and lower MTT than treated lymphoma nodes. So, PCT may be helpful for assessment of the activity of lymphoma and identification of residual activity after treatment (Fig. 7).
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Fig. 6. Untreated non-Hodgkin lymphoma. (a) Contrast CT scan shows enlarged left submandibular lymph node. (b) BF map shows increased blood flow of the enlarged lymph node (BF is 144.6 ml/100 g/min). (c) BV map shows increased BV of the enlarged lymph node (BV is 8.4 ml/100 g).
3.3. Malignant versus benign head and neck tumors In a previous study on benign and malignant head and neck tumors, MTT could differentiate between malignant and benign lesions with all lesions having MTT of 3.5 s or less being malignant and no malignancies showing MTT of 5.5 s or more [19]. A study on PCT of parotid tumors reported increased BF and BV in parotid tumors compared to normal parotid tissue. The MTT was lower in parotid tumors than that in normal tissue and PS was elevated. Interestingly, the BF and BV values were significantly higher in benign (Fig. 8) than malignant parotid tumors. The proposed cause of this finding might be the higher cellularity-stromal grade in benign than malignant tumors as well as microfoci of necrosis in malignant tumors [46]. 4. Advantages and limitations The advantages of perfusion CT include its widespread availability, speed of image acquisition, relative lower cost compared with MR imaging, and ease of patient monitoring. Furthermore, both
conventional morphologic assessment with CT and physiologic assessment with PCT can be made during the same examination. Thus, it can be incorporated into routine CT scan to improve radiologist confidence in image interpretation and the follow-up of patients [7–11]. A major concern of PCT is the risk of exposure to ionizing radiation, especially in patients who require serial studies for monitoring treatment effects. Several techniques, including the use of reduced tube current and tube potential, can be employed to reduce radiation dose. Likewise, protocol modifications involving the use of higher temporal sampling rates, such as scanning every 2–3 s and limiting the scan duration of cine acquisition to 40–50 s, can substantially minimize the radiation exposure, as reported in studies on cerebral PCT [47,48]. Moreover, the recent use of iterative reconstruction methods instead of the routine filtered back projection methods has successfully resulted in CT radiation dose reduction while maintaining the image quality [49]. This method can potentially reduce radiation dose in PCT as well. There is limited z-axis coverage of the organ or site for dynamic acquisition, because a maximum of 4 cm of tissue can be covered
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Fig. 8. Pleomorphic adenoma. (a) CT image shows ROI is drown around the left parotid tumor. (b) BF map shows increased perfusion within the tumor with high BF flow. The BF within the tumor is 210 ml/min/100 g and of normal muscle is 27 ml/min/100 g. Fig. 7. Treated lymphoma. (a) On follow up CT there are still enlarged lymph nodes in the posterior triangle on both sides. (b) BF map shows there is no increased BF of the enlarged lymph nodes, regions of interest 5 and 6. Blood flow is 11 and 28 ml/100 g/min compared to normal muscles that is 10.5 ml/100 g/min.
investigations exploring the use of dual-energy in dynamic perfusion are recommended. 6. Conclusion
with 64-slice CT scanners. The recent introduction of CT scanners with 128, 256, and 320 detector rows allow the potential for overcoming this limitation [8–12].
5. Future directions Further applications of higher multidetector CT scanners (128 and 256 detectors) with even wider z-axis coverage (up to 16 cm) can enabling whole-CTP of head and neck within a single tube rotation [10]. Integrated applications of PCT scan with PET–CT systems will allow combined assessment of perfusion and glucose metabolism of tumors, thus enabling more understanding of the biologic behavior of tumors in vivo, information which is important both for research and clinical applications [50]. Dual-energy CT represents another break-through in CT technology that allows iodine quantification or iodine distribution maps, which is an indirect measurement of perfusion at a single time point [51,52]. Future
We conclude that PCT may have a role in management of patients with head and neck cancer as it helps in delineation of HNSCC extent, detection of metastatic lymph nodes, prediction of treatment response, differentiating recurrence from post-treatment changes and monitoring patients with HNSCC and lymphoma after therapy. Further studies on PCT of head and neck tumors are recommended because of the wide potential applications. Conflicts of interest The authors have no conflicts of interest. This includes financial or personal relationships that inappropriately influence (bias) his or her actions. References [1] Walden M, Aygun N. Head and neck cancer. Semin Roentgenol 2013;48:75–86.
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[31] Jo SY, Wang PI, Nör JE, et al. CT perfusion can predict overexpression of CXCL8 (interleukin-8) in head and neck squamous cell carcinoma. AJNR 2013, http://dx.doi.org/10.3174/ajnr.A3610. [32] Hermans R, Meijerink M, Van den Bogaert W, et al. Tumor perfusion rate determined noninvasively by dynamic computed tomography predicts outcome in head-and-neck cancer after radiotherapy. Int J Radiat Oncol Biol Phys 2003;57:1351–6. [33] Bisdas S, Nguyen SA, Anand SK, et al. Outcome prediction after surgery and chemoradiation of squamous cell carcinoma in the oral cavity, oropharynx, and hypopharynx: use of baseline perfusion CT microcirculatory parameters versus tumor volume. Int J Radiat Oncol Biol Phys 2009;73: 1313–8. [34] Cao Y, Popovtzer A, Li D, et al. Early prediction of outcome in advanced headand-neck cancer based on tumor blood volume alterations during therapy: a prospective study. Int J Radiat Oncol Biol Phys 2008;72:1287–90. [35] Zima A, Carlos R, Gandhi D, et al. Can pretreatment CT perfusion predict response of advanced squamous cell carcinoma of the upper aerodigestive tract treated with induction chemotherapy? AJNR 2007;28:328–34. [36] Truong M, Saito N, Ozonoff A, et al. Prediction of locoregional control in head and neck squamous cell carcinoma with serial CT perfusion during radiotherapy. AJNR 2011;32:1195–201. [37] Abdel Razek AA, Kandeel AY, Soliman N, et al. Role of diffusion-weighted echo-planar MR imaging in differentiation of residual/recurrent head and neck tumors and post-treatment changes. AJNR 2007;28:1146–52. [38] Bisdas B, Rumboldt Z, Wagenblast J, et al. Response and progression-free survival in oropharynx squamous cell carcinoma assessed by pretreatment perfusion CT: comparison with tumor volume measurements. AJNR 2009;30: 793–9. [39] Jin G, Su D, Liu L, et al. The accuracy of computed tomographic perfusion in detecting recurrent nasopharyngeal carcinoma after radiation therapy. J Comput Assist Tomogr 2011;35:26–30. [40] Gandhi D, Chepeha DB, Miller T, et al. Correlation between initial and early follow-up CT perfusion parameters with endoscopic tumor response in patients with advanced squamous cell carcinomas of the oropharynx treated with organ-preservation therapy. AJNR 2006;27:101–6. [41] Petralia G, Preda L, Giugliano G, et al. Perfusion computed tomography for monitoring induction chemotherapy in patients with squamous cell carcinoma of the upper aerodigestive tract: correlation between changes in tumor perfusion and tumor volume. J Comput Assist Tomogr 2009;33:552–9. [42] Surlan-Popovic K, Bisdas S, Rumboldt Z, et al. Changes in perfusion CT of advanced squamous cell carcinoma of the head and neck treated during the course of concomitant chemoradiotherapy. AJNR 2010;31:570–5. [43] Abramyuk A, Wolf G, Shakirin G, et al. Preliminary assessment of dynamic contrast-enhanced CT implementation in pretreatment FDG-PET/CT for outcome prediction in head and neck tumors. Acta Radiol 2010;51: 793–9. [44] Bisdas S, Fetscher S, Feller A, et al. Primary B cell lymphoma of the sphenoid sinus: CT and MRI characteristics with correlation to perfusion and spectroscopic imaging features. Eur Arch Otorhinolaryngol 2007;264: 1207–13. [45] Dugdale PE, Miles KA, Bunce I, et al. CT measurement of perfusion and permeability within lymphoma masses and its ability to assess grade, activity, and chemotherapeutic response. J Comput Assist Tomogr 1999;23:540–7. [46] Bisdas S, Baghi M, Wagenblast J, et al. Differentiation of benign and malignant parotid tumors using deconvolution-based perfusion CT imaging: feasibility of the method and initial results. Eur J Radiol 2007;64:258–65. [47] Wintermark M, Smith WS, Ko NU, et al. Dynamic perfusion CT: optimizing the sampling interval and contrast volume for calculation of perfusion CT parameters in stroke patients. AJNR 2004;25:720–9. [48] Wiesmann M, Berg S, Bohner G, et al. Dose reduction in dynamic perfusion CT of the brain: effects of the scan frequency on measurements of cerebral blood flow, cerebral blood volume, and mean transit time. Eur Radiol 2008;18:2967–74. [49] Vachha B, Brodoefel H, Wilcox C, et al. Radiation dose reduction in soft tissue neck CT using adaptive statistical iterative reconstruction (ASIR). Eur J Radiol 2013, http://dx.doi.org/10.1016/j.ejrad. [50] Veit-Haibach P, Schmid D, Strobel K, et al. Combined PET/CT-perfusion in patients with head and neck cancers. Eur Radiol 2013;23:163–73. [51] Tawfik AM, Kerl JM, Razek AA, et al. Image quality and radiation dose of dualenergy CT of the head and neck compared with a standard 120-kVp acquisition. AJNR 2011;32:1994–9. [52] Tawfik AM, Razek AA, Kerl JM, et al. Comparison of dual-energy CTderived iodine content and iodine overlay of normal, inflammatory and metastatic squamous cell carcinoma cervical lymph nodes. Eur Radiol 2013, http://dx.doi.org/10.1007/s00330-013-3035-3.
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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Review
Perfusion CT of head and neck cancer夽 Ahmed Abdel Khalek Abdel Razek ∗ , Ahmed Mohamed Tawfik, Lamiaa Galal Ali Elsorogy, Nermin Yehia Soliman Diagnostic Radiology Department, Mansoura Faculty of Medicine, Mansoura 13551, Egypt
a r t i c l e
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Article history: Received 12 September 2013 Received in revised form 5 December 2013 Accepted 8 December 2013 Keywords: Perfusion CT Head and neck Squamous cell carcinoma Recurrence
a b s t r a c t We aim to review the technique and clinical applications of perfusion CT (PCT) of head and neck cancer. The clinical value of PCT in the head and neck includes detection of head and neck squamous cell carcinoma (HNSCC) as it allows differentiation of HNSCC from normal muscles, demarcation of tumor boundaries and tumor local extension, evaluation of metastatic cervical lymph nodes as well as determination of the viable tumor portions as target for imaging-guided biopsy. PCT has been used for prediction of treatment outcome, differentiation between post-therapeutic changes and tumor recurrence as well as monitoring patient after radiotherapy and/or chemotherapy. PCT has a role in cervical lymphoma as it may help in detection of response to chemotherapy and early diagnosis of relapsing tumors. © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Head and neck cancer accounts for up to 5–10% of all cancers. The most common pathologic type (90%) is squamous cell carcinoma. The diagnostic work-up of head and neck cancer relies on CT and MRI, and the main clinical value is staging the disease by accurately determining tumor volume, assessing its extension and detection of lymph node metastases. Conventional CT and MRI, however, provide mainly anatomic information and rely on morphologic changes with very little information about tumor physiology or functional behavior [1–3]. Functional MR imaging modalities such as diffusion MR imaging, dynamic susceptibility perfusion contrast MR imaging and MR spectroscopy [4–6] as well as positron-emission tomography (PET) have been applied to investigate head and neck cancer [7]. PCT has been used to obtain measures of tumor vascular physiology and hemodynamics. The basic principle of PCT is recording time changes in X-ray attenuation over a fixed area of interest during passage of a fast bolus of iodinated contrast medium through the region. The dynamic acquisitions cover the first pass of
Abbreviations: BF, blood flow; BV, blood volume; CM, contrast medium; EGFR, epidermal growth factor receptor; MTT, mean transit time; MVD, microvessel density; HNSCC, head and neck squamous cell carcinoma; PCT, perfusion CT; ROI, region of interest; PS, permeability surface area product; TAC, time attenuation curve; SCC, squamous cell carcinoma; VEGFR, vascular endothelial growth factor. 夽 Presented as educational exhibit at American Society of Neuroradiology (ASNR) 2012. ∗ Corresponding author. Tel.: +20 161948567; fax: +20 502315105. E-mail addresses: [email protected] (A.A.K.A. Razek), ahm m tawfi[email protected] (A.M. Tawfik), [email protected] (L.G.A. Elsorogy), nermin [email protected] (N.Y. Soliman). 0720-048X/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejrad.2013.12.008
iodinated contrast medium in the regional vascular bed, during which it has an intravascular distribution. Mathematical analysis of data obtained from PCT allows an objective measurement of tissue perfusion imaging biomarkers [8–11]. Several studies have discussed the potential applications of PCT in oncology in different regions of the body [9–11], as well as in head and neck tumors [12–14]. Tumor angiogenesis is the process of development of new capillary beds in tumors and is necessary for tumor growth and metastatic spread [11,12]. Tumors cannot grow beyond 0.1–0.2 mm in size without the induction of angiogenesis. Angiogenesis plays an important role in HNSCC. Histopathologic evaluation of biomarkers of angiogenesis such as microvessel density (MVD) and epidermal growth factor receptor (EGFR) is expensive, invasive and not widely practiced techniques [8–12]. The principles for computation of perfusion parameters for MR and CT are similar. However, there are several differences in technique. The most important advantage of PCT is the linear relationship between contrast concentration and attenuation in CT, which facilitates quantitative (versus relative) measurement of BF and BV. This is in contrast to the non-linear (logarithmic) relation between signal intensity and concentration of paramagnetic contrast medium in MR perfusion. MR perfusion is also limited by its poor reproducibility caused by differences in pulse sequences and MRI hardware as well as its greater susceptibility to image artifacts caused by metal or air–bone interfaces. Other advantages of PCT include higher spatial resolution and its relative availability. The disadvantages of PCT compared to MRI include the relatively limited coverage of PCT, the use of ionizing radiation and iodinated contrast medium [10–13]. Compared to PET, PCT is more available and less expensive. PET has the advantage of whole body imaging, but represents an
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Table 1 Protocol for perfusion CT of head and neck. Non enhanced CT acquisition Coverage area: at 64 detector scanner 40 mm Dynamic CT acquisition Acquisition mode: cine mode Tube rotation time: 1 ms Acquisition parameters Tube voltage: 80 kVp for lower radiation dose Tube current: 100 mA s Slice thickness: 5 mm, 8 sections Contrast medium Method: automatic injector Volume: 40 ml Rate of injection: 6 ml/s Start of scan: 6 s after start of contrast injection End of scan: duration 55 s ROI of arterial input Site: at ICA Arterial time attenuation curve Method: automatic
extra-step in the management of HNSCC patients and is not without limitations. The role of PET in investigation of primary neck tumors or detection of metastatic lymph nodes is still not well established and until now PET is not recommended in most guidelines for routine diagnosis and staging of head and neck cancer [7]. However, PET may have an important role in monitoring treatment response and detection of recurrence. In this article, we review technique and clinical applications of PCT in head and neck cancer.
ratio decreases by only 11% [8,9]. The tube current should also be lowered as possible, either with fixed tube current settings or with automated tube current modulation techniques, which allow more homogeneous distribution of noise. Choice of slice thickness varied from 2.5 to 5 mm, depending on the scanned region. Thicker sections decrease image noise but on the expense of lower spatial resolution [13,14]. The sampling rate or temporal resolution varies according to the analytic method used. Deconvolution-based analysis requires a higher temporal resolution than studies using compartmental based analysis. Most studies on head and neck PCT were done using deconvolution-based methods and the recommended temporal resolution has been 1 image every second. A higher the temporal resolution means a greater number of data points, but it increases the radiation exposure and limits the scan range [9–13]. 2.1.4. Contrast medium administration Contrast medium (CM) with high iodine concentration (370–400 mg/L) is preferable because it produces greater tissue enhancement. The volume of contrast bolus varies between studies from 40 to 70 ml, but usually a volume of 40 ml is used. Injection rates ranging between 3.5 and 10 ml/s are typically adequate for PCT. Compartmental analytic methods require higher injection rates while deconvolution-based methods permit lower rates. To keep the contrast bolus compact, a subsequent saline flush of 20–40 ml at the same flow rate is recommended. The scan delay for cine acquisition from the start of CM injection is determined by the CM circulation time to the region of interest. Typically, a scan delay of 5–10 s is suitable [9–11].
2. Techniques
2.2. Post-processing
Perfusion CT protocol consists of a baseline unenhanced acquisition, followed by a dynamic acquisition performed during intravenous injection of contrast medium [8–10]. Table 1 shows protocol for PCT of head and neck.
2.2.1. Arterial input selection Many studies have addressed the choice of arterial input, which is an essential step for PCT calculation [15,16]. The selected artery must be perpendicular to the imaging plane and large enough to minimize partial volume effects. In PCT of the head and neck region, the choice of either the internal or external carotid has no significant effect on PCT calculations [17]. The internal carotid artery is used as the arterial input because of its better visualization, perpendicular course, and larger caliber, all of which decrease partial volume effects. It is recommended to use the artery ipsilateral to the tumor, but the use of contralateral artery is justified in case of severe tumor encasement of the ipsilateral artery. The arterial region of interest (ROI) should be inserted in a section proximal to any visible arterial plaques to avoid any errors [16,17].
2.1. Data acquisition 2.1.1. Unenhanced CT acquisition The baseline unenhanced CT acquisition serves as a localizer to select the appropriate tissue area to be included in the contrastenhanced dynamic imaging range, therefore a lower dose, thicker section scanning should be used [12]. 2.1.2. Dynamic CT acquisition The first-pass study for PCT comprises images acquired in a cine-mode (axial acquisition with continuous tube rotation without table motion) for a total of 40–60 s. For permeability measurements, a second phase is obtained after 2–10 min [12,13]. 2.1.3. Acquisition parameters Depending on the scanner configuration, a 2-cm scan range (16row CT scanner), a 4-cm scan range (64-row CT scanner) or 8–16 cm (128- or 320-row CT detector) can be selected for dynamic scanning. Selection of acquisition parameters for PCT varies according to the scanned region, the configuration of the scanner and the mathematical analysis technique used. The balance between radiation exposure, image noise, spatial and temporal resolutions is of utmost importance. To reduce radiation exposure, it is advisable to use a low tube voltage (80–100 kVp) protocol. The increase in image noise is counterbalanced by an increase in attenuation of iodine at low tube voltage, so that the signal to noise ratio is kept constant or slightly decreases [12,13]. Perfusion CT at 80 kVp decreases the radiation dose up to 300% compared to 120 kVp, while the signal to noise
2.2.2. Arterial time attenuation curve (TAC) An arterial TAC is generated after selection of the arterial ROI. The curve should contain a first-pass phase with steep rise and high peak followed by steep decay and then a small peak representing recirculation (Fig. 1). The end of first pass is defined as the lowest point reached after maximal peak and before recirculation peak. Some software packages can identify the end of first pass automatically; but the automatic identification may lead to inaccuracies and manual identification is recommended. Early or late selection of the end of first pass is associated with substantial changes in perfusion parameters [10,16]. 2.2.3. Tumor region of interest (ROI) A ROI must be inserted inside the tumor so that the software may quantify perfusion values within it. In placing the ROI, special attention should be paid to ensuring that it does not include large vessels, air or surrounding adipose tissue. It is vital that the ROI remains confined within the tumor margins in the whole dynamic perfusion series, and any subtle patient’s motion during the scan
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2.4.1. Blood flow (BF) map BF map is defined as flow rate of blood through the vasculature in tissue region. It is measured in ml/min/100 g of tissue. BF includes flow in large vessels, arterioles, capillaries, venules and veins as well as arteriovenous shunts. It represents tumor vascularity and grade. It is the most reliable parameter for differentiation of malignant from benign tumors [8,9]. 2.4.2. Blood volume (BV) map BV map is defined as the volume of blood within vasculature in a tissue region that flows. It is measured in ml/100 g of tissue. The BV includes blood in large vessels, arterioles, capillaries, venules and veins. It represents tumor vascularity [9,10]. 2.4.3. Mean transit time (MTT) map MTT map is defined as average time taken by blood elements to traverse the vasculature from the arterial end to the venous end. It is expressed in seconds. It is thought as a surrogate marker for perfusion pressure [8,9]. Fig. 1. Arterial time attenuation curve (TAC). TAC represents attenuation in the arterial input plotted against time. The first pass of contrast medium appears in the left part of curve with steep up-slope, high peak enhancement, and quick decay; and is followed by recirculation phase.
which changes the position of the ROI will cause errors in calculation. The use of manually drawn free-hand ROI traced around tumor margins is preferred to circular or oval software based ROIs because tumor perfusion is spatially heterogeneous [9,12]. The tumor ROI may be inserted in only a single section showing the maximal tumor dimensions, or alternatively in multiple sections and then average values taken. No significant differences were observed between the 2 methods in PCT of HNSCC [18]. 2.3. Analysis of perfusion CT 2.3.1. Deconvolution analysis When a contrast bolus arrives in an artery supplying a given region of the body, it undergoes delay and dispersion. Deconvolution attempts to correct for this effect. Deconvolution of the arterial input function and tissue curves can be accomplished using a variety of techniques. Singular value decomposition has yielded the most robust results from all the deconvolution methods and has gained widespread acceptance [8,9]. 2.3.2. Compartmental analysis In kinetic modeling technique, analysis can be undertaken using the single compartment or double-compartment method. The single compartmental method assumes that the intravascular and extravascular spaces are a single compartment and calculates tissue perfusion based on the conservation of mass within the system (i.e., using Fick’s principle). It estimates perfusion using the maximal slope or the peak height of the tissue concentration curve normalized to the arterial input function. Conversely, the double-compartmental method assumes that intravascular and extravascular spaces are separate compartments and estimates capillary permeability and BV using Patlak analysis, which quantifies the passage of contrast from the intravascular space into the extravascular space [10,11]. 2.4. Parametric perfusion maps Compartmental based software produces perfusion maps (BF, BV and MTT). While deconvolution based software can also generate PS map [12] (Fig. 3).
2.4.4. Permeability surface area product (PS) PS is product of permeability and the total surface area of capillary endothelium in a unit mass of tissue (usually 100 g of tissue). It is expressed in ml/min/100 g. Measurement of PS is a surrogate marker for immature leaky vessels [10,11]. 3. Clinical applications 3.1. Head and neck squamous cell carcinoma 3.1.1. Differentiation of HNSCC from normal muscles HNSCC demonstrates increased CP, BF, BV, and decreased MTT compared with normal tissue or benign lesions. Many studies on PCT of HNSCC demonstrated significant increase in BF, BV, and PS together with significant reduction in MTT in HNSCC as compared to adjacent normal muscle [19–21] (Fig. 2). 3.1.2. Extension of HNSCC CTP can differentiate HNSCC from adjacent normal muscles. This difference can aid in delineation of the outlines of the tumor from adjacent soft tissue. Also, it helps to detect extensions of the tumor and infiltration of the surrounding soft tissue. Accurate detection of tumor extension in the head and neck is important for tumor staging [22,23] (Fig. 3). 3.1.3. Metastatic cervical lymph nodes Presence of metastatic lymph nodes in patients with HNSCC changes the tumor stage, treatment strategy and significantly worsens the prognosis [24,25]. Characterization of cervical lymph nodes in patients with HNSCC is difficult by cross-sectional anatomic and functional MR imaging. In one study, metastatic lymph nodes (Fig. 4) had higher perfusion than benign nodes, although the difference was not significant [26]. In another study, BF, BV and PS were significantly higher for metastatic nodes in hypopharyngeal and laryngeal carcinoma compared to benign cervical lymph nodes [27]. 3.1.4. Guidance for biopsy PCT maps can differentiate viable from necrotic regions of HNSCC and other malignant tumors of head and neck. The viable regions of malignancy show high BF and BV, while the necrotic regions display low BF and BV. This has the potential for guiding biopsy to the region with highest BF and BV on PCT maps, thus can help in reducing sampling errors [28].
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Fig. 2. Retromolar trigone squamous cell carcinoma. (a) Contrast CT image shows a region of interest drawn within the tumor in the right retromolar trigone. The tumor cannot be well delineated from surrounding soft tissue. (b) BF map shows high BF of the tumor as demonstrated by light blue and green colors; compared to the surrounding muscles with darker blue colors. Quantitative BF of the tumor is 86.6 ml/min/100 g compared to 12.1 ml/min/100 g in the muscles.
3.1.5. Biomarker of angiogenesis It was found that increased blood flow on PCT is correlated with angiogenesis and increased tumor vascularity, and increased tumor vascularity is associated with local recurrence and metastasis [29–31]. The BF and BV of HNSCC correlated positively with MVD, indicating the potential of PCT for assessing angiogenesis [29]. A significant correlation was detected between PCT measures and epidermal growth factor receptor (EGFR) overexpression in HNSCC, suggesting that PCT may be used for monitoring molecular biomarkers. EGFR is considered a risk factor for recurrence and disease-specific death in HNSCC [30]. In another study, there was a significant positive correlation between relative blood flow, measured by PCT and interleukin-8 level in patients with HNSCC. Because interleukin-8 is a biomarker of increased angiogenesis, PCT may be used in HNSCC patients for prediction of increased angiogenesis and tumor aggressiveness and selection of patients who may benefit from treatment with antiangiogenic drugs [31]. 3.1.6. Prediction of response to radio- and chemotherapy Few studies discussed the prediction of response of HNSCC to radio and chemotherapy with PCT [32–36]. Low perfusion of HNSCC is associated with higher rates of local failure of radiation therapy [34]. PCT may be able to identify patients who will successfully respond to induction chemotherapy, which could potentially
Fig. 3. Left supraglottic squamous cell carcinoma. (a) Contrast CT image showing a region of interest drawn within the tumor in the left aryepiglottic fold. (b) BV map shows high BV of the tumor as demonstrated by green, yellow and red colors; compared to the surrounding muscles with blue colors. Quantitative BV of the tumor is 5.4 ml/100 g compared to 1.1 ml/100 g in the muscles.
eliminate this step for subsequent patients when deciding on the appropriate treatment regimen [35]. PCT parameters can be regarded as an independent predictor of local failure in irradiated HNSCC. In a previous study, the pretreatment tumor BF and capillary permeability were significantly higher in patients who achieved locoregional control than those with treatment failure [36]. 3.1.7. Differentiation of recurrence from post therapeutic changes Post-therapeutic changes are difficult to differentiate from tumor recurrence on conventional CT or MRI, because they show a similar degree of enhancement [37]. In a study on SCC of the oral cavity and oropharynx after chemo-radiation treatment, there was no statistical difference in perfusion parameters between primary and recurrent tumors. Recurrent disease could be differentiated on
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Fig. 4. Metastatic cervical lymph node. (A) Contrast CT scan shows enlarged metastatic lymph node infiltrating left sternocleidomastoid muscle. (B) BV map shows high perfusion in the metastatic left cervical lymph node as compared to healthy contralateral muscle. BV of metastatic node is 5.5 ml/100 g compared to 1.3 ml/100 g in muscle.
the basis of significantly higher BF from post-therapeutic changes [38]. In another study on nasopharyngeal carcinoma treated with radiotherapy, recurrent tumors had significantly higher BF, BV and PS than post-radiation changes [39] (Fig. 5). 3.1.8. Monitoring of HNSCC after therapy The gold standard for monitoring of HNSCC after therapy is endoscopy and biopsy. Variable degrees of decrease in BV, BF and PS are observed in responders after induction chemotherapy. A statistically significant correlation was found between 20% reduction of BV at CTP and 50% reduction of tumor volume at endoscopy after chemotherapy [40]. Another study reported that after chemotherapy BF and BV significantly decreased and the MTT significantly increased in the responders group. The decrease in BF and BV correlated with tumor volume reduction after chemotherapy. No such changes are observed in non-responders [41]. The serial changes of PCT parameter after chemoradiotherapy were monitored in another study. In the responders, the perfusion parameter values
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Fig. 5. Recurrence at the right cheek after excision and radiotherapy of right maxillary carcinoma. (A) CT scan shows heterogeneous enhancement of the right maxillary sinus and surrounding tissue. (B) BF map shows high BF (84 ml/min/100 g) of the soft tissue of the right check denoting recurrence compared to low BF (13 ml/min/100 g) of the lesion in the right maxillary sinus denoting non-neoplastic inflammatory tissue.
over the course of treatment showed either a pattern of significant constant reduction (BF), of significant initial reduction followed by a plateau (BV), or non-significant fluctuations (MTT and PS). Nonresponders demonstrated an acute increase of BF, BV, and PS [42]. Also, there is correlation between CTP parameters and standardized uptake values in treatment response [43]. 3.2. Lymphoma Both Hodgkin’s disease (HD) and non-Hodgkin’s lymphoma (NHL) frequently occur in the head and neck. Marked elevation of BF, BV and PS and reduction of MTT were observed in primary sphenoid sinus lymphoma (Fig. 6) [44]. In another study, higher perfusion was observed in active lymphoma compared to inactive lymphoma. Progression of disease on serial evaluation from inactive to active was also associated with increase in perfusion [45]. Untreated lymphoma has higher BF, BV and PS and lower MTT than treated lymphoma nodes. So, PCT may be helpful for assessment of the activity of lymphoma and identification of residual activity after treatment (Fig. 7).
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Fig. 6. Untreated non-Hodgkin lymphoma. (a) Contrast CT scan shows enlarged left submandibular lymph node. (b) BF map shows increased blood flow of the enlarged lymph node (BF is 144.6 ml/100 g/min). (c) BV map shows increased BV of the enlarged lymph node (BV is 8.4 ml/100 g).
3.3. Malignant versus benign head and neck tumors In a previous study on benign and malignant head and neck tumors, MTT could differentiate between malignant and benign lesions with all lesions having MTT of 3.5 s or less being malignant and no malignancies showing MTT of 5.5 s or more [19]. A study on PCT of parotid tumors reported increased BF and BV in parotid tumors compared to normal parotid tissue. The MTT was lower in parotid tumors than that in normal tissue and PS was elevated. Interestingly, the BF and BV values were significantly higher in benign (Fig. 8) than malignant parotid tumors. The proposed cause of this finding might be the higher cellularity-stromal grade in benign than malignant tumors as well as microfoci of necrosis in malignant tumors [46]. 4. Advantages and limitations The advantages of perfusion CT include its widespread availability, speed of image acquisition, relative lower cost compared with MR imaging, and ease of patient monitoring. Furthermore, both
conventional morphologic assessment with CT and physiologic assessment with PCT can be made during the same examination. Thus, it can be incorporated into routine CT scan to improve radiologist confidence in image interpretation and the follow-up of patients [7–11]. A major concern of PCT is the risk of exposure to ionizing radiation, especially in patients who require serial studies for monitoring treatment effects. Several techniques, including the use of reduced tube current and tube potential, can be employed to reduce radiation dose. Likewise, protocol modifications involving the use of higher temporal sampling rates, such as scanning every 2–3 s and limiting the scan duration of cine acquisition to 40–50 s, can substantially minimize the radiation exposure, as reported in studies on cerebral PCT [47,48]. Moreover, the recent use of iterative reconstruction methods instead of the routine filtered back projection methods has successfully resulted in CT radiation dose reduction while maintaining the image quality [49]. This method can potentially reduce radiation dose in PCT as well. There is limited z-axis coverage of the organ or site for dynamic acquisition, because a maximum of 4 cm of tissue can be covered
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Fig. 8. Pleomorphic adenoma. (a) CT image shows ROI is drown around the left parotid tumor. (b) BF map shows increased perfusion within the tumor with high BF flow. The BF within the tumor is 210 ml/min/100 g and of normal muscle is 27 ml/min/100 g. Fig. 7. Treated lymphoma. (a) On follow up CT there are still enlarged lymph nodes in the posterior triangle on both sides. (b) BF map shows there is no increased BF of the enlarged lymph nodes, regions of interest 5 and 6. Blood flow is 11 and 28 ml/100 g/min compared to normal muscles that is 10.5 ml/100 g/min.
investigations exploring the use of dual-energy in dynamic perfusion are recommended. 6. Conclusion
with 64-slice CT scanners. The recent introduction of CT scanners with 128, 256, and 320 detector rows allow the potential for overcoming this limitation [8–12].
5. Future directions Further applications of higher multidetector CT scanners (128 and 256 detectors) with even wider z-axis coverage (up to 16 cm) can enabling whole-CTP of head and neck within a single tube rotation [10]. Integrated applications of PCT scan with PET–CT systems will allow combined assessment of perfusion and glucose metabolism of tumors, thus enabling more understanding of the biologic behavior of tumors in vivo, information which is important both for research and clinical applications [50]. Dual-energy CT represents another break-through in CT technology that allows iodine quantification or iodine distribution maps, which is an indirect measurement of perfusion at a single time point [51,52]. Future
We conclude that PCT may have a role in management of patients with head and neck cancer as it helps in delineation of HNSCC extent, detection of metastatic lymph nodes, prediction of treatment response, differentiating recurrence from post-treatment changes and monitoring patients with HNSCC and lymphoma after therapy. Further studies on PCT of head and neck tumors are recommended because of the wide potential applications. Conflicts of interest The authors have no conflicts of interest. This includes financial or personal relationships that inappropriately influence (bias) his or her actions. References [1] Walden M, Aygun N. Head and neck cancer. Semin Roentgenol 2013;48:75–86.
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