BOLD MRI of human tumor oxygenation during carbogen breathing.

An MRI method is described for demonstrating improved oxygenation of human tumors and normal tissues during carbogen inhalation (95% O2, 5% CO2). T2*-weighted gradient-echo imaging was performed before, during, and after carbogen breathing in 47 tumor patients and 13 male volunteers. Analysis of artifacts and signal intensity was performed. Thirty-six successful tumor examinations were obtained. Twenty showed significant whole-tumor signal increases (mean 21.0%, range 6.5-82.4%), and one decreased (-26.5 +/- 8.0%). Patterns of signal change were heterogeneous in responding tumors. Five of 13 normal prostate glands (four volunteers and nine patients with nonprostatic tumors) showed significant enhancement (mean 11.4%, range 8.4-14.0%). An increase in brain signal was seen in 11 of 13 assessable patients (mean 8.0 +/- 3.7%, range 5.0-11.7%). T2*-weighted tumor MRI during carbogen breathing is possible in humans. High failure rates occurred due to respiratory distress. Significant enhancement was seen in 56%, suggesting improved tissue oxygenation and blood flow, which could identify these patients as more likely to benefit from carbogen radiosensitization.

Attentional control in Alzheimer's disease.

Attentional control of executive function declines during the early stages of Alzheimer's disease. Controversy exists as to whether this decline results from a single global deficit or whether attentional control can be fractionated, with some aspects being more vulnerable than others. We investigated three proposed domains of attention, namely (i) focal attention, based on simple and choice reaction times; (ii) the capacity to resist distraction in a visual search task; and (iii) the capacity to divide attention between two simultaneous tasks. For each domain, two levels of difficulty were used to study Alzheimer's disease patients, who were compared with elderly and young control subjects. The unitary attentional hypothesis predicted that the impacts of level of difficulty, age and disease would be qualitatively similar across the three attentional domains. In fact we observed different patterns for each domain. We obtained no differential impairment for patients in the focal attentional task, whereas patients were somewhat more susceptible than control subjects to the similarity of the distractor items in visual search. Finally, we observed marked impairment in the capacity of Alzheimer's disease patients to combine performance on two simultaneous tasks, in contrast to preserved dual-task performance in the normal elderly group. These results suggest a need to fractionate executive processes, and reinforce earlier evidence for a specific dual-task processing deficit in Alzheimer's disease.

Gas exchange parameters in radiotherapy patients during breathing of 2%, 3.5% and 5% carbogen gas mixtures.

The gas mixture carbogen may be breathed by patients to enhance the oxygenation level and therefore the radiosensitivity of tumours. However, owing to the high CO2 content, its inhalation is associated with patient intolerance. Our aim was to determine a suitable carbon dioxide and oxygen gas mixture with similar enhancement of arterial oxygenation to 5% carbogen and with improved patient tolerance. 14 patients entered the study; of those 14, 8 were able to tolerate 2%, 3.5% and 5% carbogen mixtures as well as a control gas for sufficient time to allow successful arterial blood gas sampling. Gas exchange parameters were measured using a carbon dioxide monitor and a blood gas analyser. Arterial carbon dioxide tension ranged from 2.9 kPa to 6.82 kPa whilst breathing the carbogen mixtures, and arterial oxygen tension increased at least three-fold from basal values. There were no significant changes in the respiratory rate, heart rate and blood pH. The results suggest that 2% CO2 in O2 enhances arterial oxygen levels to a similar extent as 3.5% and 5% CO2 and that it is well tolerated.

Inspired and expired gas concentrations in man during carbogen breathing.

Capnometer measurements during 46 evaluable treatments in which patients were administered carbogen (95% O2, 5% CO2) have demonstrated that the mean inspired carbon dioxide level was 3.1% (range 0-4.7) and the mean inspired oxygen concentration was 70.6% (range 26.4-94). The explanation for this observation is leakage of air into the breathing system during radiotherapy.

Dynamic contrast enhanced magnetic resonance scanning as a predictor of response to accelerated radiotherapy for advanced head and neck cancer.

Tumour perfusion has been assessed in patients with advanced head and neck cancer using dynamic contrast enhanced MRI prior to and at completion of accelerated radiotherapy, and related to local tumour control. Sequential MRI scans, at 3 s intervals after intravenous injection of gadolinium using a dynamic scan sequence through a tumour region of interest (ROI), were performed in 13 patients with advanced head and neck cancer before and on completion of radiotherapy. The scans have been analysed in terms of maximum tumour enhancement (E), slope of the enhancement versus time curve and the time taken to reach maximum tumour enhancement (Tmax), and these parameters related to tumour outcome after radiotherapy. Local tumour control was related to the value of E on a post-radiotherapy scan and the difference in Tmax between a pre- and post-radiotherapy scan. Durable local control was seen in those tumours with a post-radiotherapy value for E of less than 8 and a mean fall in Tmax of 27.3 s. These results imply that tumours with diminished tumour perfusion at the end of radiotherapy are those most sensitive to treatment and that those tumours which show greater tumour enhancement after accelerated radiotherapy are likely to fail locally. This may reflect the persistence of viable perfused tumour at completion of radiotherapy.

The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging.

PURPOSE: Gradient-Recalled Echo (GRE) Magnetic Resonance Imaging (MRI), which detects changes in blood vessel deoxyhaemoglobin content, has been investigated as a noninvasive monitor of changes in human tumor oxygenation and blood flow, in response to carbogen (95% O2, 5% CO2) breathing. METHODS AND MATERIALS: GRE images (TE = 60 ms, TR = 200 ms, alpha = 40 degrees, 256[2] matrix) were acquired from 31 patients with primary and metastatic disease, prior to and during carbogen breathing. Three patients underwent a follow-up examination after radiotherapy. RESULTS: Seventeen out of 34 tumors showed enhanced image intensity, consistent with an improvement in tumor oxygenation and blood flow, while 11 showed no response; 6 studies were technical failures. In one patient a metastatic node that had eluded orthodox investigation was visualized. A reduction in response was observed in the three patients studied postradiotherapy. CONCLUSION: This method, which can be performed on a standard clinical MRI instrument, provides a noninvasive measurement of tumor response to oxygenation/blood flow modification. In principle, this should enable the clinician to optimize treatment protocols, such as carbogen breathing, for individual radiotherapy patients.

A prospective study of PET-FDG imaging for the assessment of head and neck squamous cell carcinoma.

The main aim of the study was to evaluate the use of positron emission tomography using fluoro-deoxyglucose (PET-FDG) imaging for the detection of squamous cell carcinoma of the head and neck. Fifty-four consecutive patients with malignancies involving the head and neck were studied prospectively. Thirty-one patients presented with primary disease and 23 were suspected of recurrent or residual disease. All patients underwent full clinical staging, PET-FDG scans and anatomical imaging, 37 underwent computed tomography (CT), 13 magnetic resonance (MR) and four had both CT and MR. Clinical assessment, CT/MR, PET-FDG and histological examination were all evaluated independently of each other. All 31 primary head and neck malignant tumours were detected by PET-FDG. Based on 16 patients who underwent neck dissections, the sensitivity and specificity of PET-FDG for detecting nodal disease was 67% and 100% respectively, compared with clinical assessment of 58% and 75% and CT/MR of 67% and 25%. In all 12 patients, PET-FDG correctly identified the presence of absence or recurrent or residual disease. PET-FDG staged 13 post-treatment necks with an accuracy of 100% as compared to CT/MR which was accurate in 7 of 13 and clinical assessment which was accurate in eight. Three sites of abnormal tracer uptake unrelated to malignancy were recorded as incidental findings (mandibular osteomyelitis, 1: post glossectomy site, 2). PET-FDG was more accurate than CT/MR for identifying primary and recurrent tumours as well as metastatic lesions in the neck. If these diagnostic properties of PET-FDG are confirmed in further prospective studies, it could prove a valuable adjunct for the management of head and neck cancer.

Validation and clinical application of computer-combined computed tomography and positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose head and neck images.

BACKGROUND: Positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (PET-FDG) improves the detection of head and neck squamous cell cancer (HNSCC), but lacks anatomical detail. The accuracy of registered computed tomography/magnetic resonance (CT/MR) and PET-FDG in delineation of HNSCC at the primary site and its clinical application was investigated. METHOD: Preoperatively 30 patients were staged clinically and each had either CT (23), MR (5), or both CT and MR (2) scans, as well as CT/MR-PET-FDG registration. Tumor margins or infiltration of specific anatomical landmarks on the different scans were compared and judged against histology. RESULTS: For primary tumors CT-PET-FDG (97%) and MR-PET-FDG (100%) delineated the tumor more accurately than CT (69%) or MR (40%) alone. Similarly, CT-PET-FDG (98%) and MR-PET-FDG (100%) were better than CT (70%) and MR alone (80%) in identifying tumor invasion of specific anatomical structures. Management was altered in 7 of 30 patients. The registered images were particularly useful in delineating tumor extension in the infratemporal fossa, maxilla and mandible, and identifying recurrences obscured by scar tissue. CONCLUSIONS: It is possible to accurately register CT, MR, and PET-FDG data sets in the head and neck. The initial results show that registered CT/ MR-PET-FDG images provide additional clinically relevant information over that obtained from clinical evaluation or conventional CT/MR imaging.

Pattern of disease in spinal cord compression on MRI scan and implications for treatment.

Recent trends in the management of bone metastases include the use of prophylactic bisphosphonates and low dose single fraction radiotherapy in favour of high dose fractionated radiotherapy. A recent animal model [1] suggests that cord compression is often associated with predominant soft tissue epidural disease, with bone collapse as a late event. In the present study, potential implications were investigated by retrospective evaluation of the pattern of disease on MRI scans of patients with spinal cord compression. The dominant component of spinal cord compression was determined in 62 patients. Two main patterns were identified, 45 (73%) had predominant soft tissue epidural disease and 15 (24%) had bone collapse. There were two with intrathecal deposits. The patterns were correlated with response to radiotherapy. Positive response was observed in 64% of those with soft tissue epidural disease and 27% of those with bone collapse. These data support the animal model, suggesting soft tissue epidural disease rather than collapse as the predominant cause of cord compression. This implies that prophylactic bisphosphonates alone would be unlikely to reduce the incidence of spinal cord compression. It also introduces concern about the long term safety of low dose single fraction radiotherapy for bone metastases in patients with a medium term life expectancy (e.g. > 2 years). These patients may benefit from more than a single fraction of radiotherapy to produce longer growth delay for sub-clinical epidural disease.

Comparison of arthrotomographic and magnetic resonance images of 50 temporomandibular joints with operative findings.

Arthrotomography and magnetic resonance imaging (MRI) were carried out on 50 temporomandibular joints (TMJs) in 48 patients who were being considered for surgery for clinically diagnosed internal derangement. The patients presented over a 4-year period with pain and dysfunction which had failed to respond to conservative management. Open surgery was carried out on all TMJs and operative findings compared with the results of imaging. The clinical diagnosis of internal derangement was confirmed in every case by imaging and at surgery. Arthrotomography over-diagnosed non-reducibility of an anteriorly displaced meniscus and perforation. MRI over-diagnosed non-reducibility to a lesser extent and under-diagnosed perforation. MRI demonstrated neither bony changes nor adhesions. Dynamic arthrotomography produced the best images of meniscal derangement in function and the pre-arthrogram tomograms were the best indicator of osseous abnormality. Arthrotomography was the preferred imaging technique.

Primary bone tumors. MR morphologic appearance correlated with pathologic examinations.

Eighty-three MR studies for primary bone tumors, performed with both spin echo and short time inversion recovery (STIR) sequences, were reviewed. Twenty-six patients underwent surgery within 10 days after MR imaging. Specimens were cut and directly compared with MR images. In the remainder, pathologic slides were compared in order to obtain a better understanding of MR pattern. All MR images were examined with a traditional morphologic approach and, upon comparison with surgical macroslides and with pathology samples, some MR distinctive patterns were identified: the bulky appearance of osteosarcoma surrounded by muscle edema, the multilobular high signal intensity (SI) chondroid lesions, the subtle infiltration of Ewing's sarcoma, rarely accompanied by muscle edema and prone to MR underestimation, the well defined "multiple shells" pattern of giant cell tumor, and the ill defined "storiform" appearance of malignant fibrous histocytoma are all typical MR features strictly corresponding to pathologic findings. The chondroid origin tumors may be identified based on the lobular high SI pattern whereas a benign fibrous lesion was the only one in this series to be distinguished relying on the SI. Peritumoral soft tissue edema was found by the STIR sequence only in malignant tumors (69%) of this series, and particularly in osteosarcoma (96%), chondrosarcoma (83%), and giant cell tumor (100%): this associate finding may further contribute to the diagnosis.

MRI in primary bone tumors: therapeutic implications.

The accuracy of preoperative MRI in detecting tumor extent has been evaluated in 35 patients with primary bone neoplasms; intra-osseous extent was measured on MR images and compared with macroslides of surgical specimens in 26 cases. An almost completely accurate prediction of tumor size was obtained with the combined employment of Spin-Echo (SE) and Short Inversion Time Inversion Recovery (STIR) sequences in the various tumors, with the exception of two Ewing's sarcomas. Changes in Signal Intensity (SI) and tumor morphology were identified in those cases which had undergone presurgical chemotherapy; the reduction in SI and in tumor size or the appearance of a more homogeneous signal was correlated with a positive response to cytotoxic therapy. MR imaging fully satisfies surgeon's preoperative requirements in the assessment of therapy-responding neoplasms as well as in local tumor staging in all types of neoplasms, with the exception of Ewing's sarcoma.

The role of the STIR sequence in magnetic resonance imaging examination of bone tumours.

Sixty patients with primary bone tumours were evaluated with magnetic resonance imaging (MRI) at 0.5 T with both conventional spin-echo (SE) and short inversion time inversion recovery (STIR) sequences. The results have been reviewed in order to evaluate the accuracy of STIR and conventional SE sequences in the detection of tumours, the definition of intramedullary extent and soft-tissue involvement. The intraosseous neoplastic extent has been compared with macroslides of surgical specimens in 24 cases. The role of the STIR sequence in detection of recurrences in the post-surgical follow-up was also evaluated. The STIR sequence, designed to suppress signal from fat, also enhances the signal from tissue with long T1 and T2 relaxation times, such as neoplastic and inflammatory tissue. The STIR sequence with T1 of 120-130 ms in all cases suppressed the high signal from fatty bone marrow, giving a clear depiction of tumour extent, in both its intramedullary and soft-tissue components, and is superior to conventional SE images. The high sensitivity (100% of our cases) of this technique is counterbalanced by its lack of specificity: on STIR sequences both tumour and peritumorous oedema give an increase of signal intensity, limiting assessment of tumour extent. Peritumoral oedema, only present in our series in malignant neoplasms, may however be differentiated on the basis of the configuration of the abnormal areas, and by comparing STIR images with short repetition time/echo time sequence results.

Use of high resolution in vivo volume selected 1H-magnetic resonance spectroscopy to investigate leukemia in humans.

In vivo high resolution volume-selected 1H magnetic resonance spectroscopy of human tibia has been undertaken using spatial coordinates obtained from magnetic resonance images. Adult tibial marrow has a 1H spectrum rich in fatty acid resonances and is readily distinguished from the 1H spectra of surrounding leg muscle. In all four leukemic patients examined, infiltration of fat cells of tibial marrow by proliferating cells rich in mobile H2O protons was evident by magnetic resonance imaging. Selective examination of volumes of tibial marrow (1 cm3) by 1H magnetic resonance spectroscopy confirmed marked differences in the 1H spectra of marrow from these patients. Increases in the H2O peak of the 1H spectra were correlated with infiltration of blast cells and lack of control of the neoplastic disease. These studies are the first to report the use of volume selected magnetic resonance spectroscopy to selectively monitor leukemia in humans.