Novel imaging techniques in refractory pituitary adenomas.

Accurate localization of the site(s) of active disease is key to informing decision-making in the management of refractory pituitary adenomas when autonomous hormone secretion and/or continued tumor growth challenge conventional therapeutic approaches. In this context, the use of non-standard MR sequences, alternative post-acquisition image processing, or molecular (functional) imaging may provide valuable additional information to inform patient management.

Modern imaging in Cushing's disease.

Management of Cushing's disease is informed by dedicated imaging of the sella and parasellar regions. Although magnetic resonance imaging (MRI) remains the investigation of choice, a significant proportion (30-50%) of corticotroph tumours are so small as to render MRI indeterminate or negative when using standard clinical sequences. In this context, alternative MR protocols [e.g. 3D gradient (recalled) echo, with acquisition of volumetric data] may allow detection of tumors that have not been previously visualized. The use of hybrid molecular imaging (e.g. 11C-methionine positron emission tomography coregistered with volumetric MRI) has also been proposed as an additional modality for localizing microadenomas.

11C-methionine PET aids localization of microprolactinomas in patients with intolerance or resistance to dopamine agonist therapy.

PURPOSE: To assess the potential for 11C-methionine PET (Met-PET) coregistered with volumetric magnetic resonance imaging (Met-PET/MRCR) to inform clinical decision making in patients with poorly visualized or occult microprolactinomas and dopamine agonist intolerance or resistance. PATIENTS AND METHODS: Thirteen patients with pituitary microprolactinomas, and who were intolerant (n = 11) or resistant (n = 2) to dopamine agonist therapy, were referred to our specialist pituitary centre for Met-PET/MRCR between 2016 and 2020. All patients had persistent hyperprolactinemia and were being considered for surgical intervention, but standard clinical MRI had shown either no visible adenoma or equivocal appearances. RESULTS: In all 13 patients Met-PET/MRCR demonstrated a single focus of avid tracer uptake. This was localized either to the right or left side of the sella in 12 subjects. In one patient, who had previously undergone surgery for a left-sided adenoma, recurrent tumor was unexpectedly identified in the left cavernous sinus. Five patients underwent endoscopic transsphenoidal selective adenomectomy, with subsequent complete remission of hyperprolactinaemia and normalization of other pituitary function; three patients are awaiting surgery. In the patient with inoperable cavernous sinus disease PET-guided stereotactic radiosurgery (SRS) was performed with subsequent near-normalization of serum prolactin. Two patients elected for a further trial of medical therapy, while two declined surgery or radiotherapy and chose to remain off medical treatment. CONCLUSIONS: In patients with dopamine agonist intolerance or resistance, and indeterminate pituitary MRI, molecular (functional) imaging with Met-PET/MRCR can allow precise localization of a microprolactinoma to facilitate selective surgical adenomectomy or SRS.

Prospective study evaluating the relative sensitivity of 18F-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and 99mTc-MDP bone scintigraphy, using an adaptive trial design.

BACKGROUND: The detection of occult bone metastases is a key factor in determining the management of patients with renal cell carcinoma (RCC), especially when curative surgery is considered. This prospective study assessed the sensitivity of (18)F-labelled sodium fluoride in conjunction with positron emission tomography/computed tomography ((18)F-NaF PET/CT) for detecting RCC bone metastases, compared with conventional imaging by bone scintigraphy or CT. PATIENTS AND METHODS: An adaptive two-stage trial design was utilized, which was stopped after the first stage due to statistical efficacy. Ten patients with stage IV RCC and bone metastases were imaged with (18)F-NaF PET/CT and (99m)Tc-labelled methylene diphosphonate ((99m)Tc-MDP) bone scintigraphy including pelvic single photon emission computed tomography (SPECT). Images were reported independently by experienced radiologists and nuclear medicine physicians using a 5-point scoring system. RESULTS: Seventy-seven lesions were diagnosed as malignant: 100% were identified by (18)F-NaF PET/CT, 46% by CT and 29% by bone scintigraphy/SPECT. Standard-of-care imaging with CT and bone scintigraphy identified 65% of the metastases reported by (18)F-NaF PET/CT. On an individual patient basis, (18)F-NaF PET/CT detected more RCC metastases than (99m)Tc-MDP bone scintigraphy/SPECT or CT alone (P = 0.007). The metabolic volumes, mean and maximum standardized uptake values (SUV mean and SUV max) of the malignant lesions were significantly greater than those of the benign lesions (P < 0.001). CONCLUSIONS: (18)F-NaF PET/CT is significantly more sensitive at detecting RCC skeletal metastases than conventional bone scintigraphy or CT. The detection of occult bone metastases could greatly alter patient management, particularly in the context when standard-of-care imaging is negative for skeletal metastases.

A radiologist's guide to small bowel and multivisceral transplantation.

This review will describe the indications for the various small bowel containing transplants. The importance of early referral will be highlighted. Radiologists play a central role in assessing these complex patients prior to transplantation. Furthermore, in the postoperative period, radiologists play an important part in diagnosing and treating complications.

Temozolomide responsiveness in aggressive corticotroph tumours: a case report and review of the literature.

Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard chemotherapy regimens showing limited efficacy. Recent evidence suggests that temozolomide (TMZ), an orally-active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. A low level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) predicts TMZ responsiveness in glioblastomas, and a similar correlation has been observed in the majority of aggressive pituitary adenomas/carcinomas reported to date. Here, we report a case of a silent pituitary corticotroph adenoma, which subsequently re-presented with Cushing's syndrome due to functioning hepatic metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ therapy (200 mg/m² for 5 days every 28 days-seven cycles) resulted in marked clinical, biochemical [>50% fall in adrenocorticotrophic hormone (ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral adrenalectomy. However, despite reintroduction of TMZ therapy (further eight cycles) ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ therapy in glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of pituitary adenomas/carcinomas are also considered.

Colorectal liver metastases: Current management and future perspectives.

The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation.

16 detector multislice CT versus skeletal scintigraphy in the diagnosis of wrist fractures: value of quantification of 99Tcm-MDP uptake.

To compare the measured uptake of 99Tcm-methylene diphosphonate (99Tcm-MDP) in those scaphoid fractures seen on both 16 detector multislice CT and scintigraphy, with those seen only on scintigraphy. Over a 12 month period a total of 51 patients with suspected fracture underwent both conventional 99Tcm-MDP scintigraphy and 16 detector multislice CT on the same day. The 99Tcm-MDP uptake was then quantified in patients with identified fracture. This was measured by placing a region of interest (ROI) over the fracture site and the mean and maximum number of counts were compared with those in a similar size ROI placed over background bone activity. A total of 23 fractures were identified on scintigraphy of which 16 were also detected on CT (concordant). In seven cases the fracture was not seen on CT, even in retrospect (discordant). In the discordant cases, follow-up radiographs and MRI (where available) also failed to demonstrate a fracture. The mean fracture count to background bone activity ratio averaged 7.7 (range 3.2-18.5) for concordant fractures and 3.8 (range 1.7-5.3) for discordant fractures (t-test p=0.04). The maximum fracture count to background bone activity ratio averaged 12.7 (range 4.3-27.7) for concordant fractures and 6.3 (range 2.6-9.5) for discordant fractures (t-test p=0.03). It is speculated whether these discordant fractures with less 99Tcm-MDP uptake may represent a less severe injury such as bone bruise.

Case report: False negative 16 detector multislice CT for scaphoid fracture.

We discuss a case of a 19-year-old man with scaphoid trauma. We describe the imaging findings on three sets of radiographs, bone scintigraphy, CT and MRI. CT failed to identify a scaphoid fracture, which was present on 6 week radiographs, MRI and scintigraphy. The case illustrates that despite multidetector technology, CT still relies upon cortical and or trabecular displacement to demonstrate fractures.

Hepatocellular carcinoma tumour thrombus in a re-canalised para-umbilical vein: detection by 18-fluoro-2-deoxyglucose positron emission tomography imaging.

This case report describes an unusual site of tumour thrombus in a re-canalised para-umbilical vein, in a patient with hepatocellular carcinoma (HCC) and cirrhosis. The tumour thrombus was suspected on conventional radiography and confirmed using PET imaging, illustrating the complimentary value of structural and functional imaging in achieving the correct diagnosis.

Polycystic kidneys and renal transplant imaging.

Renal transplantation is an ever-increasing procedure. Baseline DTPA renography is routinely performed in these patients in many centers to assess transplant perfusion and function. This report describes 2 cases of unusual appearance at renography resulting from the native polycystic kidneys.

Large renal cell carcinoma isometabolic with normal liver on F-18 FDG PET scan.

Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) is a very effective imaging modality in the diagnosis, staging, and monitoring of a variety of malignant conditions. The principle of imaging is based on the enhanced utilization of glucose by cancer. In this report, we describe a patient with renal cell carcinoma who showed FDG uptake isometabolic to normal liver.

A simple processing method allowing comparison of renal enhancing volumes derived from standard portal venous phase contrast-enhanced multidetector CT images to derive a CT estimate of differential renal function with equivalent results to nuclear medicine quantification.

As iodinated contrast medium is cleared by glomerular filtration, it should be possible to apply the same principles utilized in radionuclide studies to derive differential renal function by comparison of enhancing renal volumes derived from contrast enhanced multidetector CT (CEMDCT). Having established a technique iteratively which appeared successful, a retrospective study was performed using 25 consecutive patients with a wide range of urological conditions who had undergone both CEMDCT, including the renal area in the portal venous phase, and nuclear medicine (NM) assessment of renal function with no urological intervention between the studies. Proprietary volume software was used to quantify the volume and attenuation of each kidney, the products of which (after subtraction of soft tissue attenuation derived from a region of interest over psoas) gave right and left enhancing renal volumes. The contribution by each kidney as a percentage of total renal enhancing tissue was derived. Comparison with NM studies resulted in excellent correlation of relative renal function by CEMDCT and NM assessments having a regression of near unity and a Pearson's correlation coefficient of 0.96. Bland Altman and Passing Bablock tests confirmed good agreement between the two methods with no bias. This is a simple, practicable processing technique using standard portal venous phase CEMDCT images to quantify differential function. This technique may allow a one-stop CT assessment of both anatomy and function.

16-Detector multislice CT in the detection of stress fractures: a comparison with skeletal scintigraphy.

AIMS: To test the hypothesis that the improved resolution afforded by 16-detector computed tomography (CT) would translate to better stress fracture detection when compared with skeletal scintigraphy. MATERIALS AND METHODS: Thirty-three cases of suspected stress fractures in 26 patients were investigated using skeletal scintigraphy and 16-detector CT performed on the same day. Planar images of the lower limbs were taken 3h post-injection of 400MBq (99m)Tc-methylene diphosphonate ((99m)Tc-MDP). (99m)Tc-MDP uptake was quantified at suspected fracture sites. CT was performed using a 16-detector multisection machine employing 0.75mm detectors and images reconstructed in 0.5mm increments. Examinations were reported independently and discordant results were compared at follow-up. RESULTS: At initial reporting scintigraphy identified fractures in 13 of the 33 cases and CT identified four of the 33. In one case, on review of the CT images, a fracture was present in the distal fibula that was not initially identified. This resulted in eight scintigraphic-positive CT-negative discordant cases. The (99m)Tc-MDP uptake was significantly lower in the discordant fracture group compared with the concordant group (p<0.01). CONCLUSIONS: Despite technological advances in CT, scintigraphy appeared to detect more stress fractures. As such, multidetector CT should not be used as a routine initial investigation in stress fracture detection. The potential use of (99m)Tc-MDP quantification at fracture sites is of interest and may be worth further investigation.

Imaging of malignant infantile osteopetrosis before and after bone marrow transplantation.

BACKGROUND: Malignant infantile osteopetrosis (MIOP) is a sclerosing bone disease caused by absence or defective function of osteoclasts. Since these are of haemopoietic origin, the disease can be cured by allogeneic stem-cell transplantation, but there are no detailed studies of radiological follow-up of these procedures. OBJECTIVE: To investigate the radiological findings at presentation and follow-up in children undergoing bone marrow transplantation (BMT) for MIOP. MATERIALS AND METHODS: Examination of the records and imaging studies of nine paediatric patients undergoing BMT for MIOP during 1988-2000. RESULTS: Presentation findings included characteristic features such as fractures, subperiosteal new bone formation and rachitic appearances. Five children engrafted successfully, allowing assessment of the nature and speed of resolution of radiological features after transplantation. CONCLUSIONS: Radiological improvement was apparent within 2 months of successful engraftment with almost complete resolution of abnormalities after 1 year. Studies in two children who are, respectively, 58 and 83 months post-transplant show complete resolution of all bone changes.

Kallmann's syndrome: is it always for life?

OBJECTIVE: Kallmann's syndrome (KS) is defined by the association of olfactory deficit with irreversible, congenital gonadotrophin deficiency (IHH). We present evidence for the existence of a variant form of KS, in which endogenous gonadotrophin secretion recovers spontaneously in later life. DESIGN: Longitudinal clinical study. PATIENTS: Five men with anosmia or severe hyposmia, who originally presented in their late teens or early twenties as a result of severe pubertal delay and were thus presumed to have KS. RESULTS: Spontaneous onset of endogenous gonadotrophin secretion, evidenced by progressive normalization of testicular volume and of serum testosterone concentration, occurred in these men over a period of years following the initial diagnosis. CONCLUSIONS: This variant form of Kallman's syndrome is not well recognized and may well be under-diagnosed. Once full virilization has been induced, males with congenital gonadotrophin deficiency whose testes have significantly increased in size should be reassessed, off androgen replacement therapy, to identify those who no longer require treatment.