Functional computed tomography in oncology

Functional Computed Tomography (CT) describes the use of existing technologies and conventional contrast agents to capture physiological parameters that reflect the vasculature within tumours and other tissues. The technique is readily incorporated into routine conventional CT examinations and, in tumours, the physiological parameters obtained provide an in-vivo marker of angiogenesis. As well as providing a research tool, functional CT has clinical applications in tumour diagnosis, staging, risk stratification and therapy monitoring, including the characterisation of pulmonary nodules, detection of occult hepatic metastases, grading of cerebral glioma and monitoring of anti-angiogenesis drugs. With the recent commercial availability of appropriate software and the development of multislice CT systems, functional CT is poised to make a significant impact upon the imaging of patients with cancer.     

Functional CT in a rabbit model: evaluation of the perfusion characteristics before and after Ar-He cryoablation therapy

The objective of this study was to investigate the perfusion characteristics of rabbit liver tumours before and after Ar-He (argon-helium) cryoablation using functional CT and to evaluate the therapeutic effect of Ar-He cryoablation. VX-2 tumour was implanted into the livers of 30 New Zealand white rabbits. Two weeks after tumour implantation, Ar-He cryoablation was performed on these rabbits. Functional CT was performed on the rabbits before and after treatment on days 1, 5, 14, 21 and 35. In the meantime, five rabbits were killed, and the livers were removed for histopathological examination at each of the time points mentioned above. Perfusion characteristics of the tumour and hot spot, such as blood flow (BF), blood volume (BV) and permeability, were analysed based on multislice CT. Histopathological studies corresponding to functional CT were observed, and the therapeutic effects (whether the tumour disappeared completely or still remained) were judged. The two-tailed student's t-test was used to compare the differences between the effect of pre- and post-Ar-He cryoablation treatment on tumour perfusion parameters. After cryoablation treatment, the number of tumours exhibiting complete necrosis was 13 (52%), and their perfusion parameters, such as BF, BV and permeability values, were significantly lower than those before treatment (P < 0.05, P < 0.01 and P < 0.05, respectively). After treatment, the number of incomplete necrotic tumours was 12 (48%). In the earlier stage (within 14 days of treatment), the whole tumour perfusion parameters of BF, BV and permeability were significantly lower than those before treatment (P < 0.05). In the late stage (more than 14 days of treatment), the whole tumour perfusion parameters of BF, BV and permeability were not significantly different compared with the pretreatment results (P > 0.05). The hot spot perfusion parameters of incomplete necrotic tumours, such as BF, BV and permeability values, showed no significant differences compared with pretreatment (P > 0.05). Functional CT can measure the perfusion characteristics of hepatic tumours and is consistent with histopathological changes in the tumour after Ar-He cryoablation. Functional CT might also be accurate in judging the therapeutic effect of Ar-He cryoablation.     

Application of Computed Tomography for Differential Diagnosis of Glioma Stoke and Simple Cerebral Hemorrhage

Objective: To explore the value of computed tomography (CT) in the differential diagnosis of glioma strokeand simple cerebral hemorrhage. Materials and Methods: A total of 45 patients with glioma stroke and strokeas the initial symptom in our hospital from Jun., 2009 to Oct., 2013 were selected along with 50 individuals withsimple cerebral hemorrhage in the same period randomly collected as a control group. The CT results in bothgroups were analyzed and compared. Results: In the observation group, there were 25 patients with astrocytoma(55.6%), 11 with oligodendroglioma (24.4%), 8 with ependymoma (17.2%) and 1 with glioblastoma multiforma(GBM, 2.22%). Additionally, the major CT manifestation was coexistence of hemorrhage and tumor signs. Bycomparison, it could be found that the proportions of patients respectively with peripheral edema and spaceoccupyingeffect in the observation group were significantly higher than in the control group (P<0.01). Conclusions:Application of CT examination combined with medical history in patients has very important clinical value inthe differential diagnosis of glioma stroke and simple cerebral hemorrhage.     

Complete pathological response to chemotherapy for non-small cell lung cancer demonstrated by gamma camera positron emission tomography

We report the case history of a 61-year-old female smoker who presented with an inoperable T2N2M0 squamous cell carcinoma of the right upper lobe bronchus. This was staged by computed tomography (CT), positron emission tomography (PET) using a modified dual-headed gamma camera, and mediastinoscopy. She then underwent three cycles of cisplatin-containing chemotherapy. After the chemotherapy, CT demonstrated a residual 10 mm mass in the right upper lobe and a considerable reduction in size of the mediastinal lymphadenopathy. Functional tumour imaging with PET showed no abnormality, suggesting that there was no remaining viable tumour. At right upper lobectomy a complete pathological response was confirmed. We discuss PET, the potential new applications of gamma camera technology, and the use of cisplatin-containing chemotherapy in non-small cell lung cancer.     

Cerebral infection complicating systemic aspergillosis in acute leukemia: clinical and radiographic presentation

Cerebral fungal infection is becoming an increasingly recognized entity in immunocompromised patients on post-mortem examination. In order to determine the frequency of clinically significant cerebral fungal infection and define its clinical characteristics in a cohort of immunocompromised patients at high risk of fungal infection, the records of 118 patients with acute leukemia were examined for 57 clinical and laboratory features. The characteristics of 26 patients with systemic aspergillosis and acute leukemia were compared to 92 patients with acute leukemia in a control group. Eight of 118 patients (7%) had cerebral infection (seven Aspergillus, on Candida). Patients with systemic aspergillosis were more likely than patients in the control group to have focal neurologic findings (p = 0.02), confusion (p = 0.04), and abnormal computerized tomography (CT) of the brain characterized by single or multiple, enhancing or non-enhancing hypodense lesions (p = 0.02). Patients with systemic aspergillosis were more likely to die in complete remission than patients in the control group (p = 0.003); three of six patients with aspergillosis who died in remission expired as a consequence of cerebral infection. Cerebral infection complicated systemic Aspergillus infection in seven of 26 patients (27%), versus one of 16 patients with systemic Candida infection (6%) (p = NS). The authors conclude, therefore, that systemic aspergillosis complicating acute leukemia is more likely to be associated with confusion, focal neurologic findings, and and abnormal CT scan of the brain, and that these findings suggest the presence of cerebral infection. In addition, cerebral infection commonly complicates the course of systemic aspergillosis, and is a significant cause of morbidity and mortality in patients with acute leukemia. A high index of suspicion is needed to insure early diagnosis and appropriate therapy, particularly in those who achieve remission of their leukemia.Parts of this paper have been presented at the Sixth International Symposium on Infections in the Immunocompromised Host, June 3–6, 1990, Peebles, Scotland.     

CT在脑胶质瘤卒中与单纯脑出血鉴别诊断中的应用

目的:观察和探讨CT在脑胶质瘤卒中和单纯脑出血鉴别诊断中的应用效果,以期为临床鉴别两种疾病提供客观的理论依据。方法:入选2009年1月至2015年1月于本院就诊的单纯脑出血患者30例（观察A组）和脑胶质瘤卒中患者30例（观察B组）作为研究对象,针对两组患者的临床资料和CT检查情况进行对比分析,以期为鉴别诊断做出贡献。结果:观察对比A组和B组患者脑出血情况结果,A组患者最大出血量为60ml,最小出血量为7.3ml;而B组患者最大出血量为40ml,最小出血量为3.2ml;对比分析显示,A组患者平均脑出血量明显大于B组,差异具有显著性（P＜0.05）;针对A组和B组患者的CT灌注参数进行对比分析,结果显示A组患者血流量(BF)、血容量（BV）及表面通透性（PS）值均较B组患者高,差异较显著（P＜0.05）。单纯脑出血患者CT呈现明显密度增高阴影,形状和大小多呈现基底节区出血,肾形居多,内侧明显凹陷,而外侧往往发生膨隆;脑胶质瘤卒中患者CT多呈现边界清晰的高密度血肿,多数可见肿瘤实体,出血灶形态和大小均不同,呈现不均匀性,有半数以上的患者存在明显占位效应。结论:针对脑胶质瘤卒中患者应及时采取CT检查,结合临床病史等资料进行综合鉴别诊断,尽早与单纯脑出血进行区分诊断,及时进行针对性治疗,值得临床加以重视。     

The dense basilar artery as a sign of basilar territory infarction

Three cases of basilar artery territory infarction, in which a dense basilar artery was noted, are described. The dense basilar artery was recognized on computed tomography (CT) by comparing its density with that of other unaffected intracranial vessels. This sign is thought to represent basilar thrombosis or embolism and has similarities to the dense middle cerebral artery sign. The dense basilar artery is an early sign suggesting basilar territory infarction and its use improves the CT detection of basilar territory infarction.     

Long-term observation reveals time-course-dependent characteristics of tumour vascularisation

Functional properties of tumour vasculature influence the process of metastasis and play a role in generating a heterogeneous metabolic microenvironment, which contributes to genetic instability and inefficiency of tumour therapies. Morphological and functional properties of tumour vasculature may vary from tumour onset to late-stage disease. The aim of this study was to identify the dynamic alteration in tumour microcirculation in a chronic observation model. Invasively-growing, non-disseminating, green fluorescent protein transfected, human bone marrow derived endothelial cells, were implanted into cranial windows of severe combined immunodeficient mice. Intravital fluorescence microscopy was performed over a period of 85 days to measure permeability, leucocyte-endothelial interaction (LEI) and tissue perfusion rate as functional parameters. Vessel density, branching pattern and scanning electron microscopy were monitored as morphological parameters. Concordant with an increasing count of transendothelial pores, the results show that the initial event following tumour cell implantation was a significant increase in the permeability of pre-existing vessels. The variations in newly formed vessels were characterised by sequentially-occurring functional and morphological alterations with the development of characteristics typical of tumour vessels, such as increased count of trifurcations and variation in vessel calibre by more than 100%. In parallel with the increasing vessel volume per area, the tissue perfusion rate increased until day 61. It is concluded from the step-specific sequential functional and morphological alterations that the efficiency of adjuvant therapies depends not only on their intrinsic efficiency but also on the timing of their initiation.     

The blood-brain barrier and response of C.N.S. metastases to chemotherapy

Summary A case demonstrating a differential effect of chemotherapy on a pineal metastasis and parenchymal cerebral metastases is described. At presentation, extensive metastatic small cell carcinoma of the lung was present and CT scanning showed an apparently solitary metastasis in the pineal. The clinical course and serial CT scans showed significant improvement of the pineal tumor and simultaneous development of multiple intra-cerebral metastases. This case confirms that the pineal gland is excluded from the blood-brain barrier, and indicates the clinical importance of the effect of the blood-brain barrier in the responsiveness of CNS metastases to chemotherapy.     

Imagerie fonctionnelle et métabolique en radiothérapie

These past fifteen years have seen major developments in three-dimensional conformal radiotherapy (3D-CRT), with and without intensity-modulated, respiratorygated, or image-guided techniques. However, one of the fundamental prerequisites for 3D-CRT is the determination of gross tumour volume (GTV), clinical target volume (CTV), and planning target volume (PTV), always taking into account the limitations of the radiotherapy used. Although computed tomography (CT) in the treatment position remains the gold standard in radiotherapy planning, functional imaging — including positron emission topography (PET)/CT imaging, single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and functional magnetic resonance imaging (f MRI) — provides complementary data and may contribute to improving treatment quality. Furthermore, functional imaging can be used as an aid in developing treatment strategy, as a predictive factor in tumour response, and as a tool to evaluate tumour response after RT.     

Lessons from traumatic head injury for assessing functional status after brain tumour

Assessment of global functional status plays a central role in describing outcome after traumatic head injury, but has played a relatively minor role as an endpoint in brain tumour studies. Advantages of functional status as an outcome include simplicity, objectivity, and interpretability, and it is particularly useful in conditions where cognitive impairment is common. Work in the field of traumatic brain injury, specifically on the Glasgow Outcome Scale (GOS), provides lessons in how the validity and reliability of global outcome assessment can be improved. Functional status is conceptually and empirically distinct from cognition and health-related quality of life, and neither of these can adequately substitute for it as an outcome. The strongest candidate for a global outcome measure in brain tumour work is the Karnofsky Performance Status (KPS). Many of the lessons from the GOS could be applied to improvement of KPS assessment. However, the KPS has additional limitations, particularly that it is not brain injury specific. Global functional status is potentially a useful outcome for brain tumour studies, but there is a gap in the tools currently available.     

Positron emission tomography in the management of lymphomas

Positron emission tomography is a functional imaging modality that capitalizes on biochemical changes within tumour cells to localize these changes within the body. As a functional imaging tool, unlike an anatomical imaging tool such as CT, it does not require enlargement of lymph nodes affected by disease but does require sufficient numbers of tumour cells to be present with altered biochemical function to visualize these disease sites. These changes are most commonly monitored using a glucose mimic fluorodeoxyglucose which is not only taken up into tumour cells but is trapped within these cells owing to alterations of the hexokinase and dephosphorylase enzymes. This review examines the current role of FDG PET imaging in patients with Hodgkins and Non-Hodgkins lymphoma and also speculates on future roles for this imaging modality.     

SEOM–SERAM–SEMNIM guidelines on the use of functional and molecular imaging techniques in advanced non-small-cell lung cancer

Imaging in oncology is an essential tool for patient management but its potential is being profoundly underutilized. Each of the techniques used in the diagnostic process also conveys functional information that can be relevant in treatment decision-making. New imaging algorithms and techniques enhance our knowledge about the phenotype of the tumor and its potential response to different therapies. Functional imaging can be defined as the one that provides information beyond the purely morphological data, and include all the techniques that make it possible to measure specific physiological functions of the tumor, whereas molecular imaging would include techniques that allow us to measure metabolic changes. Functional and molecular techniques included in this document are based on multi-detector computed tomography (CT), 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), magnetic resonance imaging (MRI), and hybrid equipments, integrating PET with CT (PET/CT) or MRI (PET-MRI). Lung cancer is one of the most frequent and deadly tumors although survival is increasing thanks to advances in diagnostic methods and new treatments. This increased survival poises challenges in terms of proper follow-up and definitions of response and progression, as exemplified by immune therapy-related pseudoprogression. In this consensus document, the use of functional and molecular imaging techniques will be addressed to exploit their current potential and explore future applications in the diagnosis, evaluation of response and detection of recurrence of advanced NSCLC.     

Perimesencephalic subarachnoid haemorrhage: Negative angiography and favourable prognosis

The computed tomography (CT) scans of 110 consecutive patients who presented, over a 4.5-year period, following spontaneous subarachnoid haemorrhage (SAH), were reviewed. All 110 patients also had one or more 4-vessel digital subtraction cerebral angiograms. The CT scans were reviewed in each case without knowledge of the angiographic result. In nine patients (8%), SAH was confined to the perimesencephalic area, interpeduncular cistern and/or prepontine region at CT. All nine patients had at least two, and some as many as four, negative cerebral angiograms. Eighteen of the 110 patients (16%) ultimately had negative angiography. Hence, the patients with isolated perimesencephalic haemorrhage (PMH) accounted for 50% of the negative angiograms. There was a significant association between isolated PMH and negative angiography (X²= 50.1, P < 0.005). The specificity of PMH for negative angiography was 100% (95% confidence interval (CI) = 97–100%) and the sensitivity of PMH for a negative study was 50% (95% CI = 16–84%). Six of the 110 patients had basilar artery aneurysms demonstrated angiographically as the cause of their SAH but none of these six had isolated PMH at CT. All patients with isolated PMH were alive and well at follow up and none had suffered repeat SAH or vasospasm-related ischaemic cerebral injury. Perimesencephalic haemorrhage should be distinguished from SAH in general, because of the good prognosis associated with it and the doubtful need for repeat cerebral angiography after an intitial negative study.     

Clinical imaging of cancer metastasis

Tumour imaging is an essential part of the practice of oncology, with a crucial role in screening programmes and in diagnosis and staging of established disease. Furthermore, the assessment of tumour size by imaging, usually with computer tomography (CT) scanning, is a key component in determining the tumour response to therapy both in clinical trials and in daily oncology practice. Techniques such as CT, ultrasound (US) and magnetic resonance imaging (MRI) provide high resolution anatomical images with detailed structural information. However, these imaging modalities yield limited functional information on the tumour tissues and often cannot distinguish residual disease from non-viable or necrotic tumour masses, nor can they detect minimal residual disease. In contrast, radiopharmaceutical imaging and, in particular, positron emission tomography (PET) can give some functional information about the underlying tissues. The possibility of refining these techniques and also the emergence of newer imaging modalities that can detect changes in cancers at the physiological, cellular or molecular levels, gives rise to the notion that these methods will have implications for drug development strategies and also future clinical management. In this review, we briefly discuss the current role of imaging in clinical practice, describe some of the advances in imaging modalities currently undergoing evaluation, and speculate on the future role of these techniques in developmental therapeutics programmes.     

The contribution of PET to radiation treatment planning

Advances in medical imaging have greatly enhanced the speciality of radiation oncology by allowing more healthy tissue to be speared for better tumour coverage. Positron emission tomography (PET) with the glucose analogue [18F]-fluoro-2-deoxy-D-glucose (FDG) is a functional imaging method that has become widely used in oncology over the last decade. It has been rapidly incorporated in the staging and treatment planing of many patients with cancer in several anatomic sites such as non-small cell lung carcinomas. However, the initial data were controversial by the use of non dedicated PET units, the lack of patient immobilisation for radiation therapy, or the lack of image registration for fusion PET images with computed tomography (CT). The increased number of combined PET/CT units installed and the development of new isotopes that allow advances in biological and molecular tumour and healthy tissue imaging should lead to enhanced target definition for highly conformal radiation therapy. Such developments might also allow tumour viability or healthy tissue function to be imaged, which could be used during treatment as early indicators of tumour response or healthy tissue injury, possibly leading to a change in treatment strategy based on functional and biological imaging. The contribution of PET imaging advances using FDG or new tracers for treatment planing in the new era of image guided radiation therapy will be discussed in this review.     

Early rehabilitation after surgery improves functional outcome in inpatients with brain tumours

Clinical experience suggests that application of the fundamental principles of rehabilitation medicine can improve the care of patients with cancer. Despite the high incidence of neurological and functional deficits in patients affected by brain tumours (BTs), rehabilitation treatment of this population is not as well established as it is for patients with other neurological conditions. To assess functional outcome in brain tumour inpatients who underwent early rehabilitation after surgery. 75 patients who had undergone neurosurgery for primary BTs and 75 patients affected by stroke were enrolled in a case-control study. All patients were evaluated by means of a core set of clinical scales (Functional Independence Measure, Sitting Balance score, Standing Balance score, Hauser Index, Massachusetts General Hospital Functional Ambulation Classification). Patients were evaluated before the beginning (T0) and at the end (T1) of rehabilitation treatment. The neurorehabilitation programme consisted of individual 60-min sessions of treatment, administered once a day, six days a week, for four consecutive weeks. Speech therapy was included when aphasia was diagnosed. All the measures of outcome were indicative of substantial improvements for neuro-oncological and for stroke patients (P = 0.000). Analysis of subgroups showed that patients affected by meningioma achieved better results (in efficiency terms) as regards independence in activities of daily living (P = 0.02) and mobility (P = 0.04) compared with patients affected by glioblastoma or stroke. Rehabilitation after surgery can improve functional outcome, justifying the delivery of rehabilitation services, even during the acute phase, to BTs inpatients, irrespective of tumour type.     

Molecular imaging and targeted therapies in oncology: new concepts in treatment response assessment. a collection of cases

The widespread use of several new non-cytotoxic drugs and the significant improvements in functional imaging highlights a number of difficulties in monitoring, interpreting and predicting treatment response in clinical practice. Certain guidelines for disease assessment after therapy are already available: the traditional Response Evaluation Criteria in Solid Tumours guidelines based on tumour size variations using conventional imaging technologies, the recent combined method developed by Choi and colleagues in gastrointestinal stromal tumour treated with tyrosine kinase inhibitors based on tumour density variations using computed tomography (CT), and the European Organization for Research and Treatment of Cancer criteria based on tumour glucose metabolism variations using fluorodeoxyglucose (FDG) positron emission tomography (PET). At the moment combined PET/CT response criteria are still not available. A number of new PET compounds other than FDG are also currently being developed to visualize specific cellular and molecular tumour pathways but their role in assessment and prediction of cancer treatment response has not yet been thoroughly investigated in a large series. However, in clinical practice many oncologists treat cancer patients with targeted therapies or chemotherapy and evaluate the response using conventional or functional imaging without appropriate and standardized guidelines. The aim of this study was to present a selection of clinical cases that illustrate the usefulness of new PET tracers and efficacy evaluation of new drugs. In the era of molecular imaging and molecular therapies, these cases highlight the urgency to develop new criteria for treatment assessment and the exigency of correctly interpreting the biological information obtained from new technologies, and introduce new concepts that require further investigation in clinical trials.     

Measurements of heterogeneity in gliomas on computed tomography relationship to tumour grade

To undertake a preliminary study that uses CT texture analysis (CTTA) to quantify heterogeneity in gliomas on contrast-enhanced CT and to assess the relationship between tumour heterogeneity and grade. Retrospective analysis of contrast enhanced CT images was performed in 44 patients with histologically proven cerebral glioma between 2007 and 2010. 11 tumours were low grade (Grade I = 3; Grade II, = 8) and 33 high grade (Grade III = 10, Grade IV = 23). CTTA assessment of tumour heterogeneity was performed using a proprietary software algorithm (TexRAD) that selectively filters and extracts textures at different anatomical scales between filter values 1.0 (fine detail) and 2.5 (coarse features). Heterogeneity was quantified as standard deviation (SD) with or without filtration. Tumour heterogeneity, size and attenuation were correlated with tumour grade. For each parameter, receiver operating characteristics characterised the diagnostic performance for discrimination of high grade from low grade glioma and of grade III tumours from grade IV. Further the CTTA was compared to the radiological diagnosis. Tumour heterogeneity correlated significantly with grade (SD without filtration rs = 0.664, p < 0.001, SD with coarse filtration (rs = 0.714, p < 0.001). Tumour size and attenuation showed only moderate correlations with tumour grade (rs = 0.426, p = 0.004 and rs = 0.447, p = 0.002 respectively). Coarse texture was the best discriminator between high and low grade tumours (AUC 0.832, p < 0.0001) and between grade III and grade IV gliomas (AUC = 0.878 p = 0.0001). Compared to the radiological diagnosis, CTTA further characterised the indetermined cases. By quantifying tumour heterogeneity, CTTA has the potential to provide a marker of tumour grade for patients with cerebral glioma. By differentiating between high and low grade tumours, CTTA could possibly assist clinical management.