Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI.

OBJECTIVE: To determine if functional imaging using 11C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment. DESIGN/METHODS: Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post-operative MRI, were also studied. RESULTS: Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS. CONCLUSIONS: In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy).This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. OK, ASP, NB, JDP and MG are supported by the NIHR Cambridge Biomedical Research Centre. JDP has received support by an NIHR Senior Investigator award and NIHR brain injury HTC.This is the author accepted manuscript. The final version is available from BioScientifica via https://doi.org/10.1530/EJE-16-063

High grade glioma:Imaging combined with pathological grade defines management and predicts prognosis

Introduction: There is ambiguity in pathological grading of high grade gliomas within the WHO 2000 classification, especially those with predominant oligodendroglial differentiation. Patients and methods: All adult high grade gliomas treated radically, 1996-2005, were assessed. Cases in which pathology was grade III but radiology suggested glioblastoma (GBM) were classified as 'grade III/IV'; their pathology was reviewed. Results: Data from 245 patients (52 grade III, 18 grade III/IV, 175 GBM) were analysed using a Cox Proportional Hazards model. On pathology review, features suggestive of more aggressive behaviour were found in all 18 grade III/IV tumours. Oligodendroglial components with both necrosis and microvascular proliferation were present in 7. MIB-1 counts for the last 8 were all above 14%, mean 27%. Median survivals were: grade III 34 months, grade III/IV 10 months, GBM 11 months. Survival was not significantly different between grade III/IV and GBM. Patients with grade III/IV tumours had significantly worse outcome than grade III, with a hazard of death 3.7 times higher. Conclusions: The results highlight the current inconsistency in pathological grading of high grade tumours, especially those with oligodendroglial elements. Patients with histological grade III tumours but radiological appearances suggestive of GBM should be managed as glioblastoma.</p

Acute ischaemic brain lesions in intracerebral haemorrhage : multicentre cross-sectional magnetic resonance imaging study.

Subclinical acute ischaemic lesions on brain magnetic resonance imaging have recently been described in spontaneous intracerebral haemorrhage, and may be important to understand pathophysiology and guide treatment. The underlying mechanisms are uncertain. We tested the hypothesis that ischaemic lesions are related to magnetic resonance imaging markers of the severity and type of small-vessel disease (hypertensive arteriopathy or cerebral amyloid angiopathy) in a multicentre, cross-sectional study. We studied consecutive patients with intracerebral haemorrhage from four specialist stroke centres, and age-matched stroke service referrals without intracerebral haemorrhage. Acute ischaemic lesions were assessed on magnetic resonance imaging (<3 months after intracerebral haemorrhage) using diffusion-weighted imaging. White matter changes and cerebral microbleeds were rated with validated scales. We investigated associations between diffusion-weighted imaging lesions, clinical and radiological characteristics. We included 114 patients with intracerebral haemorrhage (39 with clinically probable cerebral amyloid angiopathy) and 47 age-matched controls. The prevalence of diffusion-weighted imaging lesions was 9/39 (23%) in probable cerebral amyloid angiopathy-related intracerebral haemorrhage versus 6/75 (8%) in the remaining patients with intracerebral haemorrhage (P = 0.024); no diffusion-weighted imaging lesions were found in controls. Diffusion-weighted imaging lesions were mainly cortical and were associated with mean white matter change score (odds ratio 1.14 per unit increase, 95% confidence interval 1.02-1.28, P = 0.024) and the presence of strictly lobar cerebral microbleeds (odds ratio 3.85, 95% confidence interval 1.15-12.93, P = 0.029). Acute, subclinical ischaemic brain lesions are frequent but previously underestimated after intracerebral haemorrhage, and are three times more common in cerebral amyloid angiopathy-related intracerebral haemorrhage than in other intracerebral haemorrhage types. Ischaemic brain lesions are associated with white matter changes and cerebral microbleeds, suggesting that they result from an occlusive small-vessel arteriopathy. Diffusion-weighted imaging lesions contribute to the overall burden of vascular-related brain damage in intracerebral haemorrhage, and may be a useful surrogate marker of ongoing ischaemic injury from small-vessel damage

A role for 11C-methionine PET imaging in ACTH-dependent Cushing's syndrome

ObjectiveWe report our experience of functional imaging with11C-methionine positron emission tomography–computed tomography (PET–CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome.DesignTwenty patients with i)de novoCushing's disease (CD,n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy;n=8) or iii) ectopic Cushing's syndrome (n=2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients withde novoCD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI.MethodsAll patients underwent11C-methionine PET–CT. For pituitary imaging, co-registration of PET–CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of11C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging.ResultsIn seven of ten patients withde novoCD, asymmetric11C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal11C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome,11C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region.Conclusions11C-methionine PET–CT can aid the detection of ACTH-secreting tumours in Cushing's syndrome and facilitate targeted therapy.</jats:sec

Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI.

OBJECTIVE: To determine if functional imaging using 11C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment. DESIGN/METHODS: Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post-operative MRI, were also studied. RESULTS: Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS. CONCLUSIONS: In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy).This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. OK, ASP, NB, JDP and MG are supported by the NIHR Cambridge Biomedical Research Centre. JDP has received support by an NIHR Senior Investigator award and NIHR brain injury HTC.This is the author accepted manuscript. The final version is available from BioScientifica via https://doi.org/10.1530/EJE-16-063