Complete Evaluation of Dementia: PET and MRI Correlation and Diagnosis for the Neuroradiologist.

This article will familiarize neuroradiologists with the pathophysiology, clinical findings, and standard MR imaging and PET imaging features of multiple forms of dementia as well as new emerging techniques. Cases were compiled from multiple institutions with the goal of improved diagnostic accuracy and improved patient care as well as information about biomarkers on the horizon. Dementia topics addressed include the following: Alzheimer disease, frontotemporal dementia, cerebral amyloid angiopathy, Lewy body dementia, Parkinson disease and Parkinson disease variants, amyotrophic lateral sclerosis, multisystem atrophy, Huntington disease vascular dementia, and Creutzfeldt-Jakob disease.

Financial Management Skills in Aging, MCI and Dementia: Cross Sectional Relationship to 18F-Florbetapir PET Cortical ß-amyloid Deposition.

BACKGROUND: There is a need to more fully characterize financial capacity losses in the preclinical and prodromal stages of Alzheimer's disease (AD) and their pathological substrates. OBJECTIVES: To test the association between financial skills and cortical ß-amyloid deposition in aging and subjects at risk for AD. DESIGN: Cross-sectional analyses of data from the Alzheimer's Disease Neuroimaging Initiative (ADNI-3) study conducted across 50 plus sites in the US and Canada. SETTING: Multicenter biomarker study. PARTICIPANTS: 243 subjects (144 cognitively normal, 79 mild cognitive impairment [MCI], 20 mild AD). MEASUREMENTS: 18F-Florbetapir brain PET scans to measure global cortical ß-amyloid deposition (SUVr) and the Financial Capacity Instrument Short Form (FCI-SF) to evaluate an individual's financial skills in monetary calculation, financial concepts, checkbook/register usage, and bank statement usage. There are five sub scores and a total score (range of 0-74) with higher scores indicating better financial skill. RESULTS: FCI-SF total score was significantly worse in MCI [Cohen's d= 0.9 (95%CI: 0.6-1.2)] and AD subjects [Cohen's d=3.1(CI: 2.5-3.7)] compared to normals. Domain scores and completion times also showed significant difference. Across all subjects, higher cortical ß-amyloid SUVr was significantly associated with worse FCI-SF total score after co-varying for age, education, and cognitive score [Cohen's f2=0.751(CI: 0.5-1.1)]. In cognitively normal subjects, after covarying for age, gender, and education, higher ß -amyloid PET SUVr was associated with longer task completion time [Cohen's f2=0.198(CI: 0.06-0.37)]. CONCLUSION: Using a multicenter study sample, we document that financial capacity is impaired in the prodromal and mild stages of AD and that such impairments are, in part, associated with the extent of cortical ß-amyloid deposition. In normal aging, ß-amyloid deposition is associated with slowing of financial tasks. These data confirm and extend prior research highlighting the utility of financial capacity assessments in at risk samples.

Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study.

This study was designed to evaluate whether subjects with amyloid beta (Aß) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aß pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aß+) or negative (Aß-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aß+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aß+ MCI subjects demonstrated greater worsening compared with Aß- subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs -0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P < 0.05). Similar to MCI subjects, Aß+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aß+ AD patients showed greater declines in verbal fluency and the MMSE (P < 0.05). Aß+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aß+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aß+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aß- subjects do.

Presence of antiseptic resistance genes in porcine methicillin-resistant Staphylococcus aureus.

Numerous studies have documented the presence of methicillin-resistant Staphylococcus aureus (MRSA) in meat-producing animals, which has led to concern about its spread into the community. Disinfectants play an important role in reduction of contamination in both animal husbandry and food-preparation, helping control spread of organisms from foodstuffs, including raw meat. Plasmid-borne antiseptic resistance (AR) genes increasing tolerance to several disinfectants have been reported in S. aureus of human origin (qacA/B and smr) and from bovine, equine, and caprine staphylococcal isolates (qacG, qacH, and qacJ). This study investigated the presence of AR genes in porcine MRSA isolates. Plasmid DNA from 100 MRSA ST9 strains isolated from pig carcasses was amplified for the presence of AR genes. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) to benzalkonium chloride (BC) and chlorhexidine gluconate (CHX) were determined in AR gene-positive isolates. qacG was present in 45 strains, eight of which also harbored smr. No strains carried qacA/B, qacH or qacJ. Presence of smr increased MICs to both BC and CHX and MBCs of CHX, but qacG presence only resulted in elevated MBC for CHX. This is the first report of AR genes from a porcine source. AR gene positivity has previously been associated with methicillin resistance and AR gene presence in these strains may increase their ability to persist in the environment. Improved implementation of hygiene measures during transportation and pre- and post-slaughter should be considered to prevent spread in the community.

Prognostic significance of parameters derived from co-registered 18F-fluorodeoxyglucose PET and contrast-enhanced MRI in patients with high-grade glioma.

OBJECTIVE: The aim of this study was to determine the prognostic significance of the volume and intensity of abnormal (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) accumulation within areas of contrast enhancement on post-therapeutic volumetric MRI. METHODS: A total of 10 patients with Grade III or IV glioma were treated with resection followed by intracavitary radiation therapy with (131)I-labelled antitenascin monoclonal antibody. Patients underwent serial FDG-PET and 1.5 T MR imaging. For each patient, MR and FDG-PET image volumes at each time point were aligned using a rigid-body normalised mutual information algorithm. Contrast-enhancing regions of interest (ROIs) were defined using a semi-automated k-means clustering technique. Activity within the ROI on the co-registered PET scan was calculated as a ratio (mean activity ratio; MAR) to activity in contralateral normal-appearing white matter (NAWM). The PET lesion was defined as the portion of the ROI associated with activity greater than two standard deviations above the mean in NAWM. Survival was assessed using the logrank test. RESULTS: Larger contrast-enhancing ROIs were strongly associated with an increased MAR (r = 0.51; p<0.002). Enhancing lesions with an MAR >1.2 were associated with decreased survival (p<0.016). In nine patients who died, the MAR on PET correlated inversely with survival duration (r = -0.43; p<0.01), whereas PET lesion volume did not. CONCLUSION: Following intracavitary radiation therapy, the development of contrast-enhancing lesions that are associated with high mean FDG-PET accumulation suggests poor prognosis.

Efficiency comparison between 99m Tc-tetrofosmin and 99m Tc-sestamibi myocardial perfusion studies.

The purpose of this investigation was to compare the efficiency of two different imaging protocols using two different clinically available 99mTc labelled myocardial perfusion tracers. One thousand one hundred and thirty-four imaging studies were performed prospectively, using either 99mTc-tetrofosmin or 99mTc-sestamibi, alternating the use of each tracer for a total period of 8 months. 99mTc-tetrofosmin rest studies were performed with injections of 259MBq-370MBq and imaging 30 min later. Exercise studies were performed with injections of 777MBq-1.11GBq and imaging 20 min later. 99mTc-sestamibi studies used doses similar to those in the 99mTc-tetrofosmin studies. Imaging followed a standard procedure, at 60 min after rest injection, and 30 min after exercise. For patients undergoing pharmacological stress testing99mTc-sestamibi was imaged 45 min after injection and 99mTc-tetrofosmin was imaged 30 min after injection. Variables analysed were (1) injection-to-imaging time for the procedure, and (2) the number of repeated scans because of extra cardiac activity. The completion time for the rest study was significantly shorter for 99mTc-tetrofosmin compared to 99mTc-sestamibi (47.7+/-21.7 min vs 74.3+/-25.8 min P<0.0001). Likewise, the total study time was shorter for 99mTc-tetrofosmin compared to 99mTc-sestamibi (90+/-32.7 min vs 124+/-37 min, P<0.0001). More importantly, the number of repeated scans was higher with 99mTc-sestamibi compared to 99mTc-tetrofosmin, 21.4% vs 10%, P=0.001 for rest studies and 16.4% vs 7.9% P=0.001 [corrected] for rest and stress. It was concluded that, using a same day rest/stress protocol, 99mTc-tetrofosmin provided higher patient throughput with fewer repeat scans. These factors may be considered for efficiency improvement in nuclear cardiology laboratories using 99mTc perfusion tracers.

Positron emission tomography: brain tumors and lung cancer.

F-18 fluorodeoxyglucose positron emission tomography is a uniquely powerful diagnostic tool that noninvasively provides information that is critical to appropriate clinical management of patients with non-small cell lung cancer. Not only does the functional information provided by PET complement and clarify the anatomic information supplied by CT and MR imaging, but the superior sensitivity and negative predictive value of PET allow for improved accuracy in diagnosis, prognosis, staging, and monitoring the effects of treatment. With better information at their disposal, clinicians and patients are able to make better-informed decisions, contributing to more appropriate and more cost-effective medical care. Truly, FDG-PET has earned its place as the new standard of care in imaging non-small cell lung cancer.

Intra-operative MR guidance during trans-sphenoidal pituitary resection: preliminary results.

The use of intra-operative MR image guidance has the potential to improve the precision, extent, and safety of trans-sphenoidal pituitary resections. The trans-sphenoidal approach to pituitary surgery has been performed for some time (1--3). Until now these surgeries have relied on direct visualization without the aid of image guidance. An open-bore configuration 0.5T SIGNA SP MR system (GE Medical Systems, Milwaukee, Wisconsin) has been used to provide image guidance for seventeen trans-sphenoidal pituitary adenoma resections (4). The intra-operative MRI system allowed the radiologist to successfully direct the surgeon toward the sella turcica while avoiding the cavernous sinus, optic chiasm and other critical structures. Imaging performed during the surgery monitored the extent of resection and allowed for removal of tumor beyond the surgeon's view in seven cases. Dynamic MR imaging was used to distinguish residual tumor from normal gland and postoperative changes, permitting more precise tumor localization. A heme-sensitive long TE gradient echo sequence was used to find the presence of hemorrhagic debris. All patients tolerated the procedure well without significant complications. J. Magn. Reson. Imaging 2001;13:136-141.

Dosimetry and dose-response relationships in newly diagnosed patients with malignant gliomas treated with iodine-131-labeled anti-tenascin monoclonal antibody 81C6 therapy.

PURPOSE: The objective of this study was to perform the dosimetry and evaluate the dose-response relationships in newly diagnosed patients with malignant brain tumors treated by direct injections of (131)I-labeled 81C6 monoclonal antibody (MAb) into surgically created resection cavities (SCRCs). METHODS AND MATERIALS: Absorbed doses to the 2-cm-thick shell as measured from the margins of the resection cavity interface were estimated for 42 patients with primary brain tumors. MR images were used to assess the enhanced-rim volume as a function of time after radiolabeled MAb therapy. Biopsy samples were obtained from 15 patients and 1 autopsy. RESULTS: The average absorbed dose [range] to the 2-cm shell region was 32 [3-59] Gy. For the endpoint of minimal time to MR contrast enhancement, the optimal absorbed dose and initial dose-rate were 43 +/- 16 Gy and 0. 41 +/- 0.10 Gy/h, respectively. There was a correlation between the absorbed dose and dose rate to the shell region and biopsy outcome (tumor recurrence, radionecrosis, and tumor recurrence and/or radionecrosis). In this Phase I study, the maximum tolerated dose (MTD) was 120 mCi. At this MTD, the estimated average absorbed dose and initial dose rate to the 2-cm shell were 41 [9-89] Gy and 0.51 [0.24-1.13] Gy/h, respectively. These values are in agreement with the optimal values based on the time to MR lesion rim enhancement. CONCLUSIONS: The average absorbed dose to the 2-cm shell region varied considerably and mainly depended on cavity volume. In future clinical trials, the administered activity of (131)I-labeled 81C6 MAb may be adjusted based on cavity volume in order to deliver the optimal absorbed dose of 43 Gy rather than giving a fixed administered activity.

Registration of three-dimensional magnetic resonance and radionuclide skeletal images.

PURPOSE: To apply postprocessing techniques to register three-dimensional TI-201 bone SPECT datasets with MRI. This may provide more accurate anatomic-functional correlation when localizing active tumors. MATERIALS AND METHODS: Three-dimensional datasets were constructed from previously acquired MRIs using routine imaging protocols. Registration software was used to coregister the TI-201 SPECT studies and the MRIs in three dimensions. RESULTS: Adequate TI-201 uptake in muscles and soft tissues along with relatively low accumulation in tendons and joint spaces provided adequate landmarks for visually aligning SPECT and MRI datasets. MR abnormalities were more extensive because of surrounding reactive tissue, and more focal TI-201 uptake could be demonstrated within the region of MR signal abnormality, allowing the focal metabolically active tissue to be distinguished from adjacent edema. CONCLUSIONS: Image registration of SPECT and anatomic imaging (CT or MRI) is used routinely to evaluate functional abnormalities within the brain. This technique has now been applied to the combination of TI-201 SPECT and MR data for evaluating bone lesions and may provide additional anatomic information for localizing functional abnormalities. This may be valuable for defining targets for biopsy, planning surgical treatment, and using minimally invasive therapies.

Craniotomy for tumor treatment in an intraoperative magnetic resonance imaging unit.

OBJECTIVE: The complex three-dimensional anatomic features of the brain and its vulnerability to surgical intervention make the surgical treatment of intracranial tumors challenging. We evaluated the surgical treatment of supratentorial tumors using intraoperative magnetic resonance imaging (MRI), which provides real-time guidance, allows localization of intracranial tumors and their margins, and facilitates continuous assessment of surgical progress. METHODS: Sixty patients underwent craniotomies for tumor treatment in the General Electric intraoperative MRI unit at the Brigham and Women's Hospital (Boston, MA) during a 1-year period. The patients selected were those with intracranial tumors that were considered difficult to resect because of their locations or previous incomplete operations. Twenty-nine low-grade and 19 high-grade gliomas, 8 metastatic lesions, 2 meningiomas, 1 pineoblastoma, and 1 astroblastoma were resected. RESULTS: Tumors were accurately localized and targeted, and the extent of resection, as well as any intraoperative complications, could be immediately assessed during surgery. Marked brain shifting occurred during the procedures, and repeated intraoperative imaging allowed surgical accommodation for this shifting. In more than one-third of the cases, intraoperative imaging showed residual tumor when resection appeared complete on the basis of surgical observation alone. CONCLUSION: Intraoperative MRI is a revolutionary tool for the surgical treatment of brain tumors, providing observation of the procedure as it is being performed. With intraoperative MRI, tumor resection is safer, the extent of resection can be directly evaluated, and intraoperative complications can be noted if they occur. Outcomes after resection depend on minimizing injury to normal brain tissue and achieving maximal tumor resection. The use of intraoperative MRI directly affects these factors.

Intraoperative MR imaging guidance for intracranial neurosurgery: experience with the first 200 cases.

PURPOSE: To review preliminary experience with an open-bore magnetic resonance (MR) imaging system for guidance in intracranial surgical procedures. MATERIALS AND METHODS: A vertically oriented, open-configuration 0.5-T MR imager was housed in a sterile procedure room. Receive and transmit surface coils were wrapped around the patient's head, and images were displayed on monitors mounted in the gap of the magnet and visible to surgeons. During 2 years, 200 intracranial procedures were performed. RESULTS: There were 111 craniotomies, 68 biopsies, 12 intracranial cyst evaluations, four subdural drainages, and five transsphenoidal pituitary resections performed with the intraoperative MR unit. In each case, the intraoperative MR system yielded satisfactory results by allowing the radiologist to guide surgeons toward lesions and to assist in treatment. In two patients, hyperacute hemorrhage was noted and removed. The duration of the procedure and the complication rate were similar to those of conventional surgery. CONCLUSION: Intraoperative MR imaging was successfully implemented for a variety of intracranial procedures and provided continuous visual feedback, which can be helpful in all stages of neurosurgical intervention without affecting the duration of the procedure or the incidence of complications. This system has potential advantages over conventional frame-based and frameless stereotactic procedures with respect to the safety and effectiveness of neurosurgical interventions.

Intraoperative dynamic MRI: localization of sites of brain tumor recurrence after high-dose radiotherapy.

In patients with malignant astrocytomas or metastatic brain disease treated with high-dose radiotherapy, conventional imaging methods may not adequately distinguish recurrent tumor from radiation change. We used a fast spoiled gradient refocusing technique in the open-configuration intraoperative MR system to assess the rate of regional enhancement of the treated tumor bed and to localize specific sites for pathologic sampling to determine whether gadolinium uptake correlated with histologic data. Twenty-four patients were studied. Fourteen of 15 patients with areas of early enhancement had recurrent tumor present in histologic samples, and 8 of the remaining 9 patients had only reactive changes. Dynamic MRI was predictive of recurrent tumor (P < .0005, Fisher exact test and P < .002, Student t test). We conclude that dynamic MRI in the open-bore magnet is a promising method for localizing potential sites of active tumor growth in patients treated for malignant astrocytomas and metastatic brain lesions.

Evaluation of intracranial cysts by intraoperative MR.

Eleven patients with intracranial cystic collections were evaluated in the open-bore intraoperative MR system. In each case, the cystic collection or the surrounding cerebrospinal fluid (CSF) space was injected with .02 to .5 cc of .5 mol/l gadopentetate dimeglumine. Serial imaging was performed using T1-weighted imaging. In seven patients, free communication was demonstrated between the cystic collection and the surrounding CSF spaces. In four cases, the cyst did not communicate with the CSF; two of these were drained in the intraoperative MR system with reduction in symptoms. One patient developed an aseptic meningitis 10 days after the study, which was successfully treated with steroids; no other complications were noted. We conclude that the communication of intracranial cystic collections with the cisterns and ventricles can be safely and effectively elucidated with gadolinium injection in the intraoperative MR system.

Open-configuration MR imaging, intervention, and surgery of the urinary tract.

The open-configuration MR imaging system provides new applications both in diagnosis and in therapy of conditions in the urinary tract. In addition to conventional imaging, the open configuration permits MR imaging of patients in many positions. This has already been shown to be useful in imaging the pelvis during voiding, where a sitting position allows urodynamic evaluation. The lithotomy position can be used for imaging the prostate, which also permits procedural access. The ultimate purpose of the interventional MR imaging suite is to integrate therapeutic tools and techniques with MR imaging. From surgical planning through specialized imaging systems with minimally invasive surgical applications, new methods are being developed and implemented. This new field of image-guided therapy will require extensive clinical development and evaluation for applications in the urinary tract. This will require a large concentrated interdisciplinary effort of surgeons, radiologists, computer scientists, engineers, and physicists. Successful integration of basic research and clinical work will result in a number of cutting-edge technologies with direct clinical application in the urinary tract. Initial projects have included biopsies, endoscopies, and real-time procedural control of high-temperature and cryogenic ablations. It is anticipated that the current surge in image-guided interventions will motivate even more research activity in this field, and will ultimately define the role of MR imaging guidance in urologic intervention and surgery.

Automatic motion correction for breast MR imaging.

In 29 gadolinium-enhanced breast magnetic resonance (MR) examinations, breast motion prevented accurate and efficient image processing. To compensate for global rotations and translations, an automatic motion correction method with a ratio-variance minimization algorithm was used to align images at multiple time points through an iterative process. This method reduced breast motion and improved the accuracy and efficiency of lesion detection.

Stereoscopically guided characterization of three-dimensional dynamic MR images of the breast.

A workstation was used to postprocess volume-rendered three-dimensional (3D) dynamic contrast material-enhanced magnetic resonance (MR) images of a breast carcinoma and a breast adenoma. Use of a 3D cursor allowed stereoscopic interactive probing of specific voxels to quantify contrast enhancement over time, which was mapped to a gray scale that effectively displayed enhancement as a fourth dimension. This technique is generally applicable to any time-dependent 3D imaging modality.

A theoretical model for input impedance of interstitial microwave antennas with choke.

PURPOSE: Two important characteristics for interstitial microwave antennas used in clinical hyperthermia are: (1) a good impedance match to minimize reflected power; and (2) a good power deposition pattern which is independent of insertion depth. A major problem of the miniature coaxial dipole antennas used for interstitial hyperthermia is the fact that the impedance and power deposition patterns of these antennas change with insertion depth. One possible solution is the addition of a coaxial choke. A theoretical model for calculating the input impedance of interstitial microwave antennas having a coaxial choke is presented, which may serve as the first step in the design of such antennas. METHODS AND MATERIALS: A theoretical model for calculating the input impedance of coaxial microwave antennas with and without a choke is presented using insulated antenna theory. The theoretical model was used to calculate the input impedance of several prototype antennas having various choke and feedline dimensions, and comparison was made with experimentally measured impedance measurements in tissue-equivalent phantom. RESULTS: The choke section of the antenna is not ideal if conventional plastic insulation is used as the choke dielectric, because the desired radiating length of the antenna is significantly shorter than the quarter-wavelength in the choke dielectric. Impedance calculations based on the theoretical model correlate reasonably well with experimentally measured impedance. Based on these calculations, the effect of parameters such as choke layer thickness and choke dielectric constant are discussed for a 915 MHz antenna with choke. CONCLUSION: The theoretical model can serve as a design aid for optimizing choked microwave antenna designs, as well as predicting the impedance match of a given antenna design at a given insertion depth. The model allows the effect of some variables not accessible experimentally such as termination impedance to be studied, which may also be useful in the understanding of these antennas. Calculations are easily performed on a desktop computer.