T.C. Booth

Quantitative imaging biomarkers in neuro-oncology.

Conventional structural imaging provides limited information on tumor characterization and prognosis. Advances in neurosurgical techniques, radiotherapy planning and novel drug treatments for brain tumors have generated increasing need for reproducible, noninvasive, quantitative imaging biomarkers. This Review considers the role of physiological MRI and PET molecular imaging in understanding metabolic processes associated with tumor growth, blood flow and ultrastructure. We address the utility of various techniques in distinguishing between tumors and non-neoplastic processes, in tumor grading, in defining anatomical relationships between tumor and eloquent brain regions and in determining the biological substrates of treatment response. Much of the evidence is derived from limited case series in individual centers. Despite their added value, the effect of these techniques as an adjunct to structural imaging in clinical research and practice remains limited.

Imaging of primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) comprises 5% of all primary brain tumours. PCNSL demonstrates a variety of well-documented imaging findings, which can vary depending on immune status and histological type. Imaging features of PCNSL may overlap with other tumours and infection making definitive diagnosis challenging. In addition, several rare variants of PCNSL have been described, each with their own imaging characteristics. Advanced imaging techniques including 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)FDG) and (11)Cxa0positron-emission tomography (PET), (201)Tl single-photon emission computed tomography (SPECT), (1)H-magnetic resonance spectroscopy (MRS), and MR perfusion, have been used to aid differentiation of PCNSL from other tumours. Ultimately, no imaging method can definitively diagnose PCNSL, and histology is required.

Incidental findings found in “healthy” volunteers during imaging performed for research: current legal and ethical implications

Incidental findings found in healthy volunteers during research imaging are common and have important implications for study design and performance, particularly in the areas of informed consent, subjects rights, clinical image analysis and disclosure. In this study, we aimed to determine current practice and regulations concerning information that should be given to research subjects when obtaining consent, reporting of research images, who should be informed about any incidental findings and the method of disclosure. We reviewed all UK, European and international humanitarian, legal and ethical agencies guidance. We found that the guidance on what constitutes incidental pathology, how to recognise it and what to do about it is inconsistent between agencies, difficult to find and less complete in the UK than elsewhere. Where given, guidance states that volunteers should be informed during the consent process about how research images will be managed, whether a mechanism exists for identifying incidental findings, arrangements for their disclosure, the potential benefit or harm and therapeutic options. The effects of incidentally discovered pathology on the individual can be complex and far-reaching. Radiologist involvement in analysis of research images varies widely; many incidental findings might therefore go unrecognised. In conclusion, guidance on the management of research imaging is inconsistent, limited and does not address the interests of volunteers. Improved standards to guide management of research images and incidental findings are urgently required.

Complications of Continuous Ambulatory Peritoneal Dialysis

Continuous ambulatory peritoneal dialysis (CAPD) is used to treat end-stage renal failure in an increasing number of patients. CAPD has an advantage over hemodialysis in that it allows patients greater freedom to perform daily activities; it also provides other clinical benefits. However, the long-term effectiveness of CAPD is limited by complications, which have various causes. Complications with an infectious cause include bacterial peritonitis, tuberculous peritonitis, and infections of the catheter exit site and tunnel. Noninfectious complications include catheter dysfunction, dialysate leakage, hernias, and sclerosing encapsulating peritonitis. Many imaging modalities-radiography, ultrasonography, peritoneal scintigraphy, computed tomography (CT), and magnetic resonance (MR) imaging-are useful for characterizing these complications. CT peritoneography and MR peritoneography are techniques specifically suited to this purpose. Imaging plays a critical role in ensuring that complications are detected early and managed appropriately.

Evolution of imaging for abdominal perforation.

INTRODUCTIONnGastrointestinal (GI) perforation is a common surgical presentation. In recent years, computed tomography (CT) has been shown to be accurate for predicting the site of GI perforation, and has become the investigation of choice. However the signs may be subtle or only indirectly related to the site or aetiology of perforation.nnnSUBJECTS AND METHODSnA MEDLINE and PubMed search was performed for journals before June 2009 with MeSH major terms CT and perforation. Non-English speaking literature was excluded.nnnRESULTSnExamples of GI perforation of various aetiologies are reviewed (inflammatory, neoplastic, traumatic and iatrogenic) high-lighting characteristic CT appearances as well as pitfalls in diagnosis. Features of perforation include the presence of free gas or fluid within the supra- and/or inframesocolic compartments, segmental bowel wall thickening, bowel wall discontinuity, stranding of the mesenteric fat and abscess formation.nnnCONCLUSIONSnThese differentiating features facilitate accurate multidisciplinary pre-operative evaluation, necessary to plan patient management and potential surgical approach.

The Role of Functional Dopamine-Transporter SPECT Imaging in Parkinsonian Syndromes, Part 2

SUMMARY: The functional imaging technique most widely used in European clinics to differentiate a true parkinsonian syndrome from vascular parkinsonism, drug-induced changes, or essential tremor is dopamine-transporter SPECT. This technique commonly reports dopamine-transporter function, with decreasing striatal uptake demonstrating increasingly severe disease. The strength of dopamine-transporter SPECT is that nigrostriatal degeneration is observed in both clinically inconclusive parkinsonism and early, even premotor, disease. In this clinical review (Part 2), we present the dopamine-transporter SPECT findings in a variety of neurodegenerative diseases, including multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. The findings in vascular parkinsonism, drug-induced parkinsonism, and essential tremor are also described. It is hoped that this technique will be the forerunner of a range of routinely used, process-specific ligands that can identify early degenerative disease and subsequently guide disease-modifying interventions.

Management of incidental findings during imaging research in "healthy" volunteers: current UK practice

OBJECTIVESnIncidental findings (IF) are becoming increasingly common due to the proliferation of imaging research. IFs can be life-changing for healthy volunteers. This study examined variation in IF management in UK research studies of healthy volunteers, including comparison with ethical and legal guidelines, thus providing baseline data and informing future practice.nnnMETHODSnQuestionnaire of participant background [medical/non-medical; radiologist/non-radiologist; years as principal investigator (PI)], type of research (involving children or not), institutional policy, volunteer information, radiologist involvement in reporting scans and IF disclosure mechanisms. Investigators current and perceived ideal practice was examined. Participants were PIs performing imaging research of healthy volunteers approved by UK ethics committees (2006-2009).nnnRESULTSn63/146 (43%) surveys completed. 54/61 (88.5%) had site-specific guidelines. Information commonly provided to volunteers should IF be found: personal data (51/62; 82%), contingency plans (54/62; 87%) and disclosure to general practitioner (GP)/treating physician (47/62; 76%). PIs used different strategies for image review. Commonest: radiologist reports research scans only when researcher suspicious of IF [15/57 (26%) compared with 5/28 (16%) in ideal practice]. Commonest ideal reporting strategy: routine reporting by specialist radiologists [9/28 (29%) compared with 8/57 (14%) in current practice]. 49/56 (87.5%) have a standardised disclosure contingency plan, usually involving GP. PIs most commonly disclosed IFs to volunteers when judged relevant (27/58; 47%), most commonly face to face (22/54; 41%), by volunteers GP (26/60; 43%). Background of PI influenced consent, reporting and disclosure practice.nnnCONCLUSIONnThere is wide variation in handling IFs in UK imaging research. Much of the current practice contravenes the vague existing legal and ethical guidelines, and is unlikely to be in the best interests of volunteers or researchers.

Analysis of image heterogeneity using 2D Minkowski functionals detects tumor responses to treatment.

The acquisition of ever increasing volumes of high resolution magnetic resonance imaging (MRI) data has created an urgent need to develop automated and objective image analysis algorithms that can assist in determining tumor margins, diagnosing tumor stage, and detecting treatment response.

The imaging of conditions affecting the cavernous sinus

The cavernous sinus can be affected by a wide range of conditions including tumours, infection, inflammation, and trauma. Disease in the cavernous sinus can produce characteristic signs and symptoms, which relate to the numerous crucial structures traversing and surrounding the cavernous sinus. Imaging, with the use of different techniques, plays a crucial role in diagnosis and management. The anatomy and imaging of the different disease entities in the cavernous sinus will be reviewed.

Carbonic Anhydrase Activity Monitored In Vivo by Hyperpolarized 13C-Magnetic Resonance Spectroscopy Demonstrates Its Importance for pH Regulation in Tumors

Carbonic anhydrase buffers tissue pH by catalyzing the rapid interconversion of carbon dioxide (CO2) and bicarbonate (HCO3 (-)). We assessed the functional activity of CAIX in two colorectal tumor models, expressing different levels of the enzyme, by measuring the rate of exchange of hyperpolarized (13)C label between bicarbonate (H(13)CO3(-)) and carbon dioxide ((13)CO2), following injection of hyperpolarized H(13)CO3(-), using (13)C-magnetic resonance spectroscopy ((13)C-MRS) magnetization transfer measurements. (31)P-MRS measurements of the chemical shift of the pH probe, 3-aminopropylphosphonate, and (13)C-MRS measurements of the H(13)CO3(-)/(13)CO2 peak intensity ratio showed that CAIX overexpression lowered extracellular pH in these tumors. However, the (13)C measurements overestimated pH due to incomplete equilibration of the hyperpolarized (13)C label between the H(13)CO3(-) and (13)CO2 pools. Paradoxically, tumors overexpressing CAIX showed lower enzyme activity using magnetization transfer measurements, which can be explained by the more acidic extracellular pH in these tumors and the decreased activity of the enzyme at low pH. This explanation was confirmed by administration of bicarbonate in the drinking water, which elevated tumor extracellular pH and restored enzyme activity to control levels. These results suggest that CAIX expression is increased in hypoxia to compensate for the decrease in its activity produced by a low extracellular pH and supports the hypothesis that a major function of CAIX is to lower the extracellular pH.