Imaging techniques to evaluate the response to treatment in oncology: current standards and perspectives.

Response evaluation in solid tumours currently uses radiological imaging techniques to measure changes under treatment. Imaging requires a well-defined anatomical lesion to be viewed and relies on the measurement of a reduction in tumour size during treatment as the basis for presumed clinical benefit. However, with the development of anti-angiogenesis agents, anatomical imaging has became inappropriate as certain tumours would not reduce in size. Functional studies are therefore necessary and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), DCE-computed tomography (CT) and DCE-ultrasonography (US) are currently being evaluated for monitoring treatments. Diffusion-weighted MR imaging (DW-MRI) and magnetic resonance spectroscopy (MRS) are also capable of detecting changes in cell density and metabolite content within tumours. In this article, we review anatomical and functional criteria currently used for monitoring therapy. We review the published data on DCE-MRI, DCE-CT, DCE-US, DW-MRI and MRS. This literature review covers the following area: basic principles of the technique, clinical studies, reproducibility and repeatability, limits and perspectives in monitoring therapy. Anatomical criteria such as response evaluation criteria in solid tumours (RECIST) will require adaptation to employ not only new tools but also different complementary techniques such as functional imaging in order to monitor therapeutic effects of conventional and new anti-cancer agents.

Carotid arterial stenosis: evaluation at CT angiography with the volume-rendering technique.

PURPOSE: To determine whether computed tomographic (CT) angiography with the volume-rendering technique (VRT) can be used to accurately quantify carotid arterial stenosis and to identify occlusions. MATERIALS AND METHODS: Spiral CT was performed in 23 patients who were referred for carotid stenosis evaluation. VRT images and shaded-surface display (SSD) images of 46 carotid arterial bifurcations were compared with findings from digital subtraction angiography (DSA). RESULTS: Agreement on stenosis category between VRT CT angiography and DSA was found in 39 (85%) of the 46 carotid arteries studied. VRT CT angiography was 92% (49 of 53) sensitive and 96% (82 of 85) specific for the detection of grade 2-3 stenoses (> or = 70% stenosis). Agreement on stenosis category between SSD CT angiography and DSA was found in 38 (83%) of the 46 carotid arteries studied. SSD CT angiography was 91% (48 of 53) sensitive and 93% (79 of 85) specific for the detection of grade 2-3 stenoses. Calcified stenoses were correctly graded at VRT CT angiography in 10 of the 10 cases with heavy mural calcified plaques, while eight of the 10 stenoses were accurately quantified at SSD CT angiography. CONCLUSION: These results indicate that VRT CT angiography is as accurate as SSD CT angiography in the evaluation of carotid arterial bifurcations.

Reversible alterations in brain metabolites during therapy for disseminated nocardiosis using proton magnetic resonance spectroscopy.

We report reversible abnormalities in magnetic resonance spectra acquired from a patient with AIDS undergoing antibiotic and corticosteroid therapy for disseminated nocardiosis, a rare opportunistic infection of immunosuppressed patients which can cause cerebral abscess formation. There was no clinical, CT or MRI evidence of HIV-1 encephalitis. MR spectra were acquired before and after treatment using a two-dimensional chemical shift imaging technique (TR 1500ms, TE 130ms). Prior to treatment, a rise in the choline to creatine ratio and a reduction in the N-acetylaspartate to creatine ratio were observed in MR spectra localized to areas of the left anteromedial centrum semiovale that appeared normal on MR imaging. After 16 weeks, the patient had recovered with complete resolution of the cerebral abscesses on MRI. The MR spectral abnormalities also returned to normal. Two months later, the patient had a relapse with focal neurological signs and further abscesses were demonstrated on MRI of the brain. The patient subsequently died and histopathological and microbiological findings at autopsy confirmed the clinical picture of a recurrence of cerebral nocardiosis with no evidence of HIV-1 encephalitis. This case illustrates reversible MR-measurable metabolite changes in the brain of an HIV-seropositive patient without HIV-1 encephalitis who underwent treatment for cerebral nocardiosis.

1H MR spectroscopy of the brain in HIV-1-seropositive subjects: evidence for diffuse metabolic abnormalities.

PURPOSE: To analyze brain metabolite changes in HIV-1-seropositive subjects in order to define whether the neuronal impairment is a localized or more diffuse process. MATERIALS AND METHODS: 15 patients and 18 volunteers underwent multivoxel proton magnetic resonance (MR) spectroscopy at 1.5T. Nine patients were classified as being neuropsychiatrically unimpaired and six as having HIV-1-associated dementia on the basis of a full neuropsychological examination. Spectra were analysed from multiple voxels located in the fronto-parietal cortex and white matter at the level of centrum semiovale. RESULTS: A significant reduction in mean peak area ratios of NAA/Cr (p<0.005 in the grey matter, p<0.01 in the white matter) and an elevation in mean Cho/Cr (p<0.005 in both grey matter and white matter) were observed in patients with HIV-1-associated dementia when compared to healthy volunteers. No significant metabolite abnormalities were detected in the neuropsychiatrically unimpaired group, although there was a similar trend in the metabolite ratios. The changes in metabolite ratios were of the same order of magnitude in the cortical grey matter and subcortical white matter as in the deeper white matter in all patients. There were also no significant regional variations in mean metabolite ratios between right and left hemispheres or anterior and posterior voxels at the level of the brain studied. There were no abnormalities in Glx/Cr in any spectra analysed from either patient group. CONCLUSION: The absence of significant regional variation in metabolite ratios at the level of the centrum semiovale provides some evidence that abnormalities of cerebral metabolites in HIV-infected patients may be part of a diffuse process.

In vivo and in vitro hepatic phosphorus-31 magnetic resonance spectroscopy and electron microscopy in chronic ductopenic rejection of human liver allografts.

BACKGROUND: In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (MRS) provides non-invasive information about phospholipid metabolism. AIMS: To delineate MRS abnormalities in patients with chronic ductopenic rejection (CDR) and to characterise spectral changes by in vitro MRS and electron microscopy. PATIENTS AND METHODS: Sixteen liver transplant recipients (four with CDR; 12 with good graft function) and 29 controls (23 healthy volunteers; six patients with biliary duct strictures) were studied with in vivo 31P MRS. Peak area ratios of phosphomonoesters (PME) and phosphodiesters (PDE), relative to nucleotide triphosphates (NTP) were measured. In vitro MRS and electron microscopy were performed on biopsy specimens from five patients with CDR, freeze clamped at retransplantation. Phosphoethanolamine (PE), phosphocholine (PC), glycerophosphorylethanolamine (GPE), and glycerophosphorylcholine (GPC) concentrations were measured. RESULTS: The 12 patients with good graft function displayed no spectral abnormalities in vivo; the four patients with CDR showed significantly elevated PME:NTP (p < 0.01) and PDE:NTP ratios (p < 0.005). Patients with biliary strictures had significant differences in PME:NTP (p < 0.01) from patients with CDR, but not in mean PDE:NTP. In vitro spectra from CDR patients showed elevated PE and PC, mirroring the in vivo changes in PME, but reduced GPE and GPC concentrations were observed, at variance with the in vivo PDE findings. On electron microscopy, there was no proliferation in hepatocyte endoplasmic reticulum. CONCLUSIONS: The increase in PME:NTP reflects altered phospholipid metabolism in patients with CDR, while the increase in PDE:NTP may represent a significant contribution from bile phospholipid.

MR imaging of osteomyelitis and neuropathic osteoarthropathy in the feet of diabetics.

Distinguishing between osteomyelitis and neuropathic osteoarthropathy of the foot frequently presents a clinical and radiologic challenge in patients with diabetes. Magnetic resonance (MR) imaging was performed in 26 diabetic patients to observe changes in signal intensity in the complicated diabetic foot. In every patient with osteomyelitis (n = 13), signal intensity abnormalities were seen within the bone marrow (low signal intensity on T1-weighted images and high signal intensity on T2-weighted images in 12 cases). Most of these patients had cortical lesions (n = 9) or associated soft-tissue infection (n = 12). Normal bone marrow signal intensity was observed in three of the four patients without osteomyelitis. Characteristic MR imaging findings (decreased signal intensity in bone marrow regardless of pulse sequence) were seen in patients with chronic neuropathic osteoarthropathy (n = 7), who were easily distinguished from patients with osteomyelitis. Conversely, in patients with acutely evolving neuropathic osteoarthropathy (n = 2), signal intensity changes within the bone marrow were similar to those observed in osteomyelitis, leading to potential diagnostic pitfalls. Familiarity with MR imaging findings observed in osteomyelitis and neuropathic osteoarthropathy can help identify these two entities, allowing early diagnosis and appropriate therapy.

MR imaging and spectroscopy of the basal ganglia in chronic liver disease: correlation of T1-weighted contrast measurements with abnormalities in proton and phosphorus-31 MR spectra.

The purpose of this study was to correlate the hyperintensity in the globus pallidus seen on T1-weighted magnetic resonance imaging (MRI) of the brain in chronic liver disease with changes in metabolite ratios measured from both proton and phosphorus-31 magnetic resonance spectroscopy (MRS) localised to the basal ganglia. T1-weighted spin echo (T1WSE) images were obtained in 21 patients with biopsy-proven cirrhosis (nine Child's grade A, eight Child's grade B and four Child's grade C). Four subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, four showed evidence of subclinical hepatic encephalopathy and 13 had overt hepatic encephalopathy. Signal intensities of the globus pallidus and adjacent brain parenchyma were measured and contrast calculated, which correlated with the severity of the underlying liver disease, when graded according to the Pugh's score (p < 0.05). Proton MRS of the basal ganglia was performed in 12 patients and 14 healthy volunteers. Peak area ratios of choline (Cho), glutamine and glutamate (Glx) and N-acetylaspartate relative to creatine (Cr) were measured. Significant reductions in mean Cho/Cr and elevations in mean Glx/Cr ratios were observed in the patient population. Phosphorus-31 MRS of the basal ganglia was performed in the remaining nine patients and in 15 healthy volunteers. Peak area ratios of phosphomonoesters (PME), inorganic phosphate, phosphodiesters (PDE) and phosphocreatine relative to beta ATP (ATP) were then measured. Mean values of PME/ATP and PDE/ATP were significantly lower in the patient population. No correlation was found between the T1WSE MRI contrast measurements of the globus pallidus and the abnormalities in the metabolite ratios measured from either proton or phosphorus-31 MR spectra. Our results suggest that pallidal hyperintensity seen on T1WSE MR imaging of patients with chronic liver disease is not related to the functional abnormalities of the brain observed in hepatic encephalopathy.

Lhermitte-Duclos disease associated with syringomyelia.

A 23-year-old man presented with a 2-week history of intracranial hypertension. CT showed a large, nonenhancing cerebellar mass with surrounding calcification and displacement of the fourth ventricle. MRI revealed a septate lesion, with low signal on T1-weighted and high signal on T2-weighted images. The cerebellar tonsils were displaced below the foramen magnum and there was associated syringomyelia. The MRI features were characteristic of Lhermitte-Duclos (LD) disease (dysplastic gangliocytoma) and the diagnosis was confirmed following surgery. In this case, we emphasise the usefulness of MRI in the diagnosis of LD disease and consider the possible pathogenesis of the associated syringomyelia.

Proton magnetic resonance spectroscopy in Huntington's disease: evidence in favour of the glutamate excitotoxic theory.

The gene responsible for Huntington's disease (HD) has been located, but its action and the pathophysiology of HD remain unclear. Glutamate excitotoxicity may contribute to the striatal neurodegeneration seen in HD. We used localised proton magnetic resonance spectroscopy (MRS) of the brain to investigate five patients with early HD, one symptom-free gene carrier, and 14 healthy volunteers. Peak area ratios of choline-containing compounds (Cho), glutamine and glutamate (Glx), and N-acetyl moieties including N-acetylaspartate (NAx), relative to creatine (Cr), were calculated. Spectra were analysed from the striatum and the occipital and the temporal cortex. The HD patients all had an elevated Glx/Cr in spectra localised to the striatum, compared with healthy controls, and one patient also had an elevated thalamic Glx/Cr. The mean Glx/Cr was unaltered in the cortical spectra of HD patients. The asymptomatic gene carrier displayed no spectral abnormalities. Our findings suggest disordered striatal glutamate metabolism and may support the theory of glutamate excitotoxicity in HD.

Cirrhosis of the human liver: an in vitro 31P nuclear magnetic resonance study.

Human livers with histologically proven cirrhosis were assessed using in vitro 31P NMR spectroscopy. Spectra were compared with those from histologically normal livers and showed significant elevations in phosphoethanolamine (PE) and phosphocholine (PC) and significant reductions in glycerophosphorylethanolamine (GPE) and glycerophosphorylcholine (GPC). There were no significant differences in spectra from livers with compensated and decompensated cirrhosis. These results help to characterise the alterations in membrane metabolism in cirrhosis of the liver.

Regional variations in cerebral proton spectroscopy in patients with chronic hepatic encephalopathy.

Regional variations in proton magnetic resonance spectroscopy (MRS) were assessed in 26 patients and 14 healthy volunteers using a two dimensional chemical shift imaging technique. Patients were classified as being neuropsychiatrically unimpaired, or as having subclinical or overt chronic hepatic encephalopathy (CHE). Peak area ratios of choline (Cho), glutamine and glutamate (Glx) and N-acetylaspartate (NAA) relative to creatine (Cr) were measured. Significant reductions in mean Cho/Cr and elevations in mean Glx/Cr were observed in the patient population, which correlated with the severity of CHE. There were significant regional variations in these metabolite ratios with the mean Cho/Cr lowest in the occipital cortex and the mean Glx/Cr highest in the basal ganglia. NAA/Cr remained relatively constant in all areas of the brain analysed. The regional variation in the metabolite ratios suggests that spectral information from more than one voxel may be useful in the assessment of patients with CHE.