PET/CT in treatment response assessment in lung cancer. When should it be recommended?

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Different treatment options are now possible both for surgical candidates and for those NSCLC patients deemed not suitable for surgery. Despite the treatments available, only a limited number of less advanced stages are potentially curable, with many patients suffering local recurrence or distant metastases. FDG-PET/CT is commonly used in many centers for post-treatment evaluation, follow-up, or surveillance; Nonetheless, there is no clear consensus regarding the indications in these cases. Based upon the results of a literature review and local expertise from a large lung cancer unit, we built clinical evidence-based recommendations for the use of FDG-PET/CT in response assessment. We found that in general this is not recommended earlier than 3 months from treatment; however, as described in detail the correct timing will also depend upon the type of treatment used. We also present a structured approach to assessing treatment changes when reporting FDG-PET/CT, using visual or quantitative approaches.

Identifying and troubleshooting the pitfalls of ictal/interictal brain perfusion SPECT studies.

Epilepsy is a prevalent condition, and surgical intervention can benefit patients with refractory seizures. Single photon emission computed tomography (SPECT) using 99mTc-HMPAO or 99mTc-ECD provides assessment of regional cerebral blood flow and is the primary non-invasive approach for imaging brain perfusion in ictal and interictal states. Ictal/interictal SPECT is valuable in localising epileptogenic foci, particularly when MRI and electroencephalography are negative. However, to obtain accurate images reflecting brain perfusion in both states, meticulous preparation of the patient, timely radiotracer injection and close coordination between neurology and nuclear medicine teams are essential. Tracers also have inherent limitations, and patients may present with coexisting brain pathologies for which coregistration of SPECT images with MRI is recommended to improve diagnostic accuracy. Inconclusive SPECT findings may require repeating the exam or considering additional investigations. A comprehensive approach, considering various factors, is crucial for accurate interpretation of SPECT studies in presurgical epilepsy evaluations. This article provides a summary of the organisation and key challenges involved in conducting ictal/interictal SPECT studies, covering the entire process from a patient's hospital arrival to the integration of results within their presurgical pathway and using our experience of 182 patients over 10 years.

The role of PET in imaging of the tumour microenvironment and response to immunotherapy.

Positron emission tomography (PET) is an exquisitely sensitive molecular imaging technique with broad utility in cancer diagnosis and monitoring. Many ligands labelled with positron-emitting isotopes have been developed that are of interest in the field of cancer imaging. This review intends to provide an overview and outlook of PET in the field of oncology using radiotracers beyond that of the now widespread 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG). A particular focus is the role of PET in understanding and monitoring the tumour microenvironment (TME) in response to chemo-radiotherapy. Furthermore priority will be given to aspects where PET has provided for monitoring of the immune response to cancer including the expanding field of cancer immunotherapy and in the arena of theranostics. The development of new techniques from both preclinical and human studies will be included to give a perspective on future directions, thereby helping to illustrate the importance of PET in cancer patient management.

Assessment of Haemodynamic Response to Nonselective Beta-Blockers in Portal Hypertension by Phase-Contrast Magnetic Resonance Angiography.

A significant unmet need exists for accurate, reproducible, noninvasive diagnostic tools to assess and monitor portal hypertension (PHT). We report the first use of quantitative MRI markers for the haemodynamic assessment of nonselective beta-blockers (NSBB) in PHT. In a randomized parallel feasibility study in 22 adult patients with PHT and a clinical indication for NSBB, we acquired haemodynamic data at baseline and after 4 weeks of NSBB (propranolol or carvedilol) using phase-contrast MR angiography (PC-MRA) in selected intra-abdominal vessels. T1 mapping of liver and spleen was undertaken to assess changes in tissue composition. Target NSBB dose was achieved in 82%. There was a substantial reduction from baseline in mean average flow in the superior abdominal aorta after 4 weeks of NSBB therapy (4.49 ± 0.98 versus 3.82 ± 0.86 L/min, P = 0.03) but there were no statistically significant differences in flow in any other vessels, even in patients with >25% decrease in heart rate (47% of patients). Mean percentage change in liver and spleen T1 following NSBB was small and highly variable. In conclusion, PC-MRA was able to detect reduction in cardiac output by NSBB but did not detect significant changes in visceral blood flow or T1. This trial was registered with the ISRCTN registry (ISRCTN98001632).

Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma.

PURPOSE: Asthma is a disease of increasing worldwide importance that calls for new investigative methods. Ex vivo lung tissue is being increasingly used to study functional respiratory parameters independent of confounding systemic considerations but also to reduce animal numbers and associated research costs. In this work, a straightforward laboratory method is advanced to probe dynamic changes in gas inhalation patterns by using an ex vivo small animal ovalbumin (OVA) model of human asthma. METHODS: Hyperpolarized (hp) (129) Xe was actively inhaled by the excised lungs exposed to a constant pressure differential that mimicked negative pleural cavity pressure. The method enabled hp (129) Xe MRI of airway responsiveness to intravenous methacholine (MCh) and airway challenge reversal through salbutamol. RESULTS: Significant differences were demonstrated between control and OVA challenged animals on global lung hp (129) Xe gas inhalation with P < 0.05 at MCh dosages above 460 µg. Spatial mapping of the regional hp gas distribution revealed an approximately three-fold increase in heterogeneity for the asthma model organs. CONCLUSION: The experimental results from this proof of concept work suggest that the ex vivo hp noble gas imaging arrangement and the applied image analysis methodology may be useful as an adjunct to current diagnostic techniques. Magn Reson Med 76:1224-1235, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Hyperpolarized 83Kr magnetic resonance imaging of alveolar degradation in a rat model of emphysema.

Hyperpolarized (83)Kr surface quadrupolar relaxation (SQUARE) generates MRI contrast that was previously shown to correlate with surface-to-volume ratios in porous model surface systems. The underlying physics of SQUARE contrast is conceptually different from any other current MRI methodology as the method uses the nuclear electric properties of the spin I = 9/2 isotope (83)Kr. To explore the usage of this non-radioactive isotope for pulmonary pathophysiology, MRI SQUARE contrast was acquired in excised rat lungs obtained from an elastase-induced model of emphysema. A significant (83)Kr T1 relaxation time increase in the SQUARE contrast was found in the elastase-treated lungs compared with the baseline data from control lungs. The SQUARE contrast suggests a reduction in pulmonary surface-to-volume ratio in the emphysema model that was validated by histology. The finding supports usage of (83)Kr SQUARE as a new biomarker for surface-to-volume ratio changes in emphysema.

Pulmonary MRI contrast using Surface Quadrupolar Relaxation (SQUARE) of hyperpolarized (83)Kr.

Hyperpolarized (83)Kr has previously been demonstrated to enable MRI contrast that is sensitive to the chemical composition of the surface in a porous model system. Methodological advances have lead to a substantial increase in the (83)Kr hyperpolarization and the resulting signal intensity. Using the improved methodology for spin exchange optical pumping of isotopically enriched (83)Kr, internal anatomical details of ex vivo rodent lung were resolved with hyperpolarized (83)Kr MRI after krypton inhalation. Different (83)Kr relaxation times were found between the main bronchi and the parenchymal regions in ex vivo rat lungs. The T1 weighted hyperpolarized (83)Kr MRI provided a first demonstration of surface quadrupolar relaxation (SQUARE) pulmonary MRI contrast.

Cryogenics free production of hyperpolarized 129Xe and 83Kr for biomedical MRI applications.

As an alternative to cryogenic gas handling, hyperpolarized (hp) gas mixtures were extracted directly from the spin exchange optical pumping (SEOP) process through expansion followed by compression to ambient pressure for biomedical MRI applications. The omission of cryogenic gas separation generally requires the usage of high xenon or krypton concentrations at low SEOP gas pressures to generate hp (129)Xe or hp (83)Kr with sufficient MR signal intensity for imaging applications. Two different extraction schemes for the hp gasses were explored with focus on the preservation of the nuclear spin polarization. It was found that an extraction scheme based on an inflatable, pressure controlled balloon is sufficient for hp (129)Xe handling, while (83)Kr can efficiently be extracted through a single cycle piston pump. The extraction methods were tested for ex vivo MRI applications with excised rat lungs. Precise mixing of the hp gases with oxygen, which may be of interest for potential in vivo applications, was accomplished during the extraction process using a piston pump. The (83)Kr bulk gas phase T1 relaxation in the mixtures containing more than approximately 1% O2 was found to be slower than that of (129)Xe in corresponding mixtures. The experimental setup also facilitated (129)Xe T1 relaxation measurements as a function of O2 concentration within excised lungs.

Validating excised rodent lungs for functional hyperpolarized xenon-129 MRI.

Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp) (129)Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp (129)Xe. Straightforward hp (129)Xe MRI protocols provide residual lung volume (RV) data and permit for spatially resolved tracking of small hp (129)Xe probe volumes during the inhalation cycle. Hp (129)Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies.

Perspectives of hyperpolarized noble gas MRI beyond 3He.

Nuclear Magnetic Resonance (NMR) studies with hyperpolarized (hp) noble gases are at an exciting interface between physics, chemistry, materials science and biomedical sciences. This paper intends to provide a brief overview and outlook of magnetic resonance imaging (MRI) with hp noble gases other than hp (3)He. A particular focus are the many intriguing experiments with (129)Xe, some of which have already matured to useful MRI protocols, while others display high potential for future MRI applications. Quite naturally for MRI applications the major usage so far has been for biomedical research but perspectives for engineering and materials science studies are also provided. In addition, the prospects for surface sensitive contrast with hp (83)Kr MRI is discussed.