In vivo prostate cancer detection and grading using restriction spectrum imaging-MRI.

BACKGROUND: Magnetic resonance imaging (MRI) is emerging as a robust, noninvasive method for detecting and characterizing prostate cancer (PCa), but limitations remain in its ability to distinguish cancerous from non-cancerous tissue. We evaluated the performance of a novel MRI technique, restriction spectrum imaging (RSI-MRI), to quantitatively detect and grade PCa compared with current standard-of-care MRI. METHODS: In a retrospective evaluation of 33 patients with biopsy-proven PCa who underwent RSI-MRI and standard MRI before radical prostatectomy, receiver-operating characteristic (ROC) curves were performed for RSI-MRI and each quantitative MRI term, with area under the ROC curve (AUC) used to compare each term's ability to differentiate between PCa and normal prostate. Spearman rank-order correlations were performed to assess each term's ability to predict PCa grade in the radical prostatectomy specimens. RESULTS: RSI-MRI demonstrated superior differentiation of PCa from normal tissue, with AUC of 0.94 and 0.85 for RSI-MRI and conventional diffusion MRI, respectively (P=0.04). RSI-MRI also demonstrated superior performance in predicting PCa aggressiveness, with Spearman rank-order correlation coefficients of 0.53 (P=0.002) and -0.42 (P=0.01) for RSI-MRI and conventional diffusion MRI, respectively, with tumor grade. CONCLUSIONS: RSI-MRI significantly improves upon current noninvasive PCa imaging and may potentially enhance its diagnosis and characterization.

Novel technique for characterizing prostate cancer utilizing MRI restriction spectrum imaging: proof of principle and initial clinical experience with extraprostatic extension.

BACKGROUND: Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI). METHODS: We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique. RESULTS: 27 patients were evaluated, excluding one patient where distortion could not be performed. Preoperative standard MRI correctly identified extraprostatic the extension in two of the nine pT3 (22%) patients, whereas RSI-MRI identified EPE in eight of nine (89%) patients. RSI-MRI correctly identified pT2 disease in the remaining 18 patients. CONCLUSIONS: In this proof of principle study, we conclude that our novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging. Further translational studies of prostate RSI-MRI in the diagnosis and staging of PCa are indicated.

Quantitative measurement of blood-brain barrier permeability using perfusion-CT in extra-axial brain tumors.

Non-invasive assessment of vascular permeability is of main importance in the diagnosis, treatment and follow-up of intracranial tumors. Perfusion-CT is one of the imaging options available, which affords quantitative assessment of cerebral blood volume and blood-brain barrier permeability. Herein we report two cases of extra-axial tumors studied with perfusion-CT. Comparison with perfusion-MRI was available in one case. High permeability values, as measured by perfusion-CT, reflected the absence of blood-brain barrier in these extra-axial tumors.

Changes in the management of ALS since the publication of the AAN ALS practice parameter 1999.

OBJECTIVE: To determine if the publication in 1999 of the AAN Practice Parameter on ALS was associated with an improvement in the standard of management of the disease. METHODS: Data on 646 patients enrolled in the ALS CARE database and on 465 patients who died in the period May 2001 to November 2002 were compared with similar data obtained from the database from 1996 to May 1999. RESULTS: The specialty ALS clinics were the most important source of information about ALS. The internet was a source for 39%. The treatment of sialorrhea, pseudobulbar emotional lability, and failure of swallowing and breathing had all improved significantly in the period after the publication of the Practice Parameter. However many patients still did not receive a gastrostomy tube or non-invasive positive pressure ventilation when indicated by the Practice Parameter, mainly because of lack of patient compliance. Cost was the main reason why 41% of patients did not receive riluzole, though they spent a third of the cost of this medication on alternative medicines. CONCLUSIONS: The publication of the AAN Practice Parameter was associated with improvement in the standard of care. Most cases in the database come from specialized ALS centers, and further information on the community care of ALS patients is needed.

The novel differentiation of human blood mononuclear cells into CD1a-negative dendritic cells is stimulated in the absence of exogenous cytokines by an extract prepared from pinecones.

The production of dendritic cells, both in-vivo and in-vitro, has become the intense focus of research activities. Common to many of these production protocols is the use of cytokines, typically granulocyte-monocyte colony stimulating factor and either interleukin 4 or tumor necrosis factor alpha or a combination of all three. Herein, we report our findings that a proprietary pinecone extract is capable of in a dose-dependent manner, and in the absence of exogenous cytokines, the rapid differentiation from peripheral blood mononuclear cells of mature CD1a-negative dendritic cells.

International investigation of breast MRI: results of a multicentre study (11 sites) concerning diagnostic parameters for contrast-enhanced MRI based on 519 histopathologically correlated lesions.

A multicentre study was undertaken to provide fundamentals for improved standardization and optimized interpretation guidelines of dynamic contrast-enhanced MRI. Only patients scheduled for biopsy of a clinical or imaging abnormality were included. They underwent standardized dynamic MRI on Siemens 1.0 (163 valid lesions > or = 5 mm) or 1.5 T (395 valid lesions > or = 5 mm) using 3D fast low-angle shot (FLASH; 87 s) before and five times after standardized bolus of 0.2 mmol Gd-DTPA/kg. One-Tesla and 1.5 T data were analysed separately using a discriminant analysis. Only histologically correlated lesions entered the statistical evaluation. Histopathology and imaging were correlated in retrospect and in open. The best results were achieved by combining up to five wash-in or wash-out parameters. Different weighting of false-negative vs false-positive calls allowed formulation of a statistically based interpretation scheme yielding optimized rules for the highest possible sensitivity (specificity 30%), for moderate (50%) or high (64-71%) specificity. The sensitivities obtained at the above specificity levels were better at 1.0 T (98, 97, or 96%) than at 1.5 T (96, 93, 86%). Using a widely available standardized MR technique definition of statistically founded interpretation rules is possible. Choice of an optimum interpretation rule may vary with the clinical question. Prospective testing remains necessary. Differences of 1.0 and 1.5 T are not statistically significant but may be due to pulse sequences.

Mycophenolate (CellCept) treatment of myasthenia gravis, chronic inflammatory polyneuropathy and inclusion body myositis.

We report favorable results of the long term use of mycophenolate in the treatment of three patients with myasthenia gravis (MG), two patients with chronic inflammatory demyelinating polyneuropathy (CIDP), one patient with secondary polymyositis (PM), and one patient with inclusion body myositis (IBM). Side effects were mild. Mycophenolate appears to be a useful addition to the armamentarium of immunosuppressants for treatment of chronic immunologically mediated neuromuscular diseases.

Dysfunctional mitochondrial respiration in the wobbler mouse brain.

The involvement of mitochondrial dysfunction promoting neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), has been suggested. Histopathological and biochemical mitochondrial abnormalities have been reported in both sporadic and familial patients and suggest the contention that mitochondria may play a key role promoting ALS. Animal models of ALS provide a unique opportunity to study this incurable and fatal human disease. In the present study we tested the hypothesis that alterations in mitochondrial physiology occur in the brain of wobbler mice. No significant difference was found in the respiratory control index or adenosine diphosphate/oxygen ratio values between isolated mitochondria of wobbler and control mice. When pyruvate and malate were used as substrates, oxygen consumption was decreased significantly by approximately 33% in mitochondria isolated from wobbler mouse brain compared to controls. Oxygen consumption in the presence of ascorbate and N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) was decreased significantly by approximately 21% in wobbler brain mitochondria compared to controls, which suggests impairment in the function of complex IV. These findings are the first demonstration of mitochondrial respiratory chain dysfunction in the brain of the wobbler mouse.

Successful immunosuppressant therapy of severe progressive cerebellar degeneration and sensory neuropathy: a case report.

A 56 year old woman had a 19 month history of a severe subacute progressive cerebellar degeneration, peripheral sensory neuropathy, and urinary incontinence. She was confined to a wheelchair, needed assistance with eating, and her speech was almost unintelligible. No underlying cancer was found despite repeated investigations, and no autoantibodies were demonstrated. She received a 3-month course of intensive immunosuppressant therapy with intravenous immunoglobulin 400 mg/kg per day for 5 days every month, oral cyclophosphamide 50 mg twice or three times a day to maintain the total lymphocyte count between 500 and 750/mm(3), and prednisone 60 mg per day. She experienced dramatic subjective and objective improvement. The dysarthria and the upper extremity dysmetria disappeared, and she regained the ability to write and cook. The lower extremity ataxia improved and she became able to walk with a cane. Urinary incontinence disappeared. A trial of intensive immunosuppressant treatment is worth considering in a patient with a clinical syndrome resembling paraneoplastic disorders, even if an underlying neoplasm and autoantibodies are not demonstrated.

MR imaging evaluation of seizures.

It is imperative for a radiologist to determine the type of seizure a patient has prior to magnetic resonance (MR) imaging to optimally provide the clinician with the information he or she requires. Specifically, complex partial seizures require evaluation of the frontal lobes and the hippocampus (for mesial temporal sclerosis). These are best evaluated with fluid-attenuated inversion recovery (FLAIR) imaging; the use of intravenously administered contrast material is not required. Other types of chronic seizures are best evaluated with nonenhanced FLAIR or T2-weighted imaging for low-grade tumors, vascular malformations, gliosis after infarction, inflammation, or trauma. The presence of new-onset seizures in an adult or the worsening of chronic seizures warrants T2-weighted or FLAIR imaging and gadolinium-enhanced T1-weighted imaging (to look for primary or metastatic tumors, infections, or inflammatory lesions). If available, echo-planar diffusion imaging should be used also (to look for acute infarcts).

Hypertensive encephalopathy: complication in children treated for myeloproliferative disorders--report of three cases.

We routinely perform echo-planar diffusion-weighted sequences in all brain magnetic resonance (MR) imaging studies. When three children undergoing chemotherapy for acute leukemia presented with seizures, conventional MR images demonstrated what appeared to be acute, posterior, parasagittal infarcts. However, diffusion-weighted images were normal. These MR imaging findings were consistent with those of hypertensive encephalopathy. Early recognition and treatment of minimal hypertension in these patients allows reversal of encephalopathy.

The spectrum of chronic inflammatory demyelinating polyneuropathy.

Research criteria for the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) were proposed by an Ad Hoc Subcommittee of the American Academy of Neurology (AAN) in 1991, and since then these criteria have been widely used in clinical studies. We have been impressed by the frequent finding of electrophysiological changes of a demyelinating neuropathy in patients whose clinical presentation does not conform to the usually accepted clinical phenotype of CIDP. To determine the clinical spectrum of CIDP, we conducted a retrospective review of patients of the peripheral electrophysiology laboratory of the University of Miami-Jackson Memorial Medical Center. Diagnostic criteria for acquired demyelination of an individual nerve were adapted from the AAN research criteria for the diagnosis of CIDP (1991). Patients were accepted for inclusion when such evidence was demonstrated in at least one motor nerve or at least two sensory nerves. We then reviewed the clinical phenotype and the underlying etiology of the neuropathy in these cases. Eighty-seven patients, 63 male and 24 female, age of onset 4-84 (mean 49.3) years, met these inclusion criteria. Forty-seven patients (54%) had distinct features outside the usual clinical presentation of CIDP. Of these, 15 (17%) had predominantly distal features, 13 (15%) had exclusively sensory polyneuropathy; seven (8%) had markedly asymmetric disease, seven (8%) had associated CNS demyelination, four (5%) had predominant cranial nerve involvement, and one (1%) had only the restless legs syndrome. An associated medical condition that may have been responsible for the acquired demyelinating neuropathy was present in 60% of the patients. We conclude that spectrum of CIDP is broader than would be indicated by the strict application of the AAN research criteria, and that many of the cases meeting more liberal criteria frequently respond to immunosuppressive therapy.

Economic and outcomes assessment of magnetic resonance imaging in the evaluation of headache.

We sought to evaluate the economic impact and diagnostic utility of magnetic resonance imaging (MRI) in the management of patients with headache and nonfocal physical examinations. Computerized medical records were retrospectively reviewed of 1,233 patients presenting for MRI of headache at our institution over a 3-year period (1992-1995). Patients with focal findings at physical examination, prior brain surgery, head trauma, or immunocompromise were excluded. A model was developed to assess the cost associated with the MR test results, and actual average institutional costs of performing an examination applied. Correlative statistical analysis of referring specialties and positive tests was also performed. Three hundred twenty-eight patients who met the above criteria were retained in the sample. One hundred sixty-three patients (50%) had negative MR test results. Of the 50% of patients with positive studies, only 5 (1.5%) had clinically significant MR results. The average cost of an MR examination was 517 dollars (1998 dollars). The cost per clinically significant managed case detected was 34,535 dollars. No statistically significant difference was found among referring specialties and clinically significant MR results. Our results indicate that MRI of nonfocal headache yields a low percentage of positive clinically significant results and has limited cost-effectiveness. Referring specialty had no significant bearing on these outcomes, regardless of specialist experience.

Optimizing lesion contrast without using contrast agents.

The essence of optimizing lesion detection is increasing the signal-to-noise (S/N) for the lesion while decreasing the S/N of the background. Maneuvers which improve one aspect of lesion detection may have a deleterious effect on another. For example, thinner slices decrease partial volume averaging (important for detection of small lesions) but also decrease S/N. Attempts to increase S/N by lowering the bandwidth may increase the TE, decreasing the degree of T1-weighting. Fast spin echo (FSE) generally offers the best T2-weighting for detection of long T2 lesions. However, lesions with short T2s (due to magnetic susceptibility effects) are better detected with gradient echo techniques. Strategies which decrease background S/N include those based on chemical shift differences (ie, spectroscopic techniques like FatSat) and those based on differences in T1 (ie, inversion recovery [IR] techniques like STIR and FLAIR).

Use of contrast in MR imaging of the lumbar spine.

Gadolinium chelates are often useful in sorting out different causes of lower back pain and lumbar radiculopathy. Gadolinium is particularly useful, for example, in distinguishing recurrent disc herniation from epidural scarring in the postoperative spine. Enhancement can demonstrate nerve roots in viral or inflammatory conditions (e.g., cytomegalovirus or Guillain-Barré syndrome), and define compression resulting from herniated discs or spiral stenoses. Gadolinium enhancement also is useful in diagnosing tumors in the intramedullary space (e.g., conus ependymoma), in the extramedullary space (e.g., drop metastases, meningioma, schwannoma), and extradural space (e.g., extraosseus extension of osseus metastases or infections).

MRI of extracranial masses in children: the usefulness of gadolinium-chelate enhancement.

OBJECTIVE: This study evaluated the usefulness of gadolinium (Gd) chelates in magnetic resonance imaging (MRI) of extracranial pediatric mass lesions. MATERIALS AND METHODS: Seventy-five MRI studies were obtained on 60 children (mean age 5.06 years) with pathologically proven mass lesions. Post-contrast T1-weighted (T1W) images were compared with pre-contrast T1-weighted, T2-weighted (T2W) and both T1W and T2W images. They were evaluated for their ability to demonstrate lesion margins and extent, to add additional information, and to increase confidence in or change a diagnosis. In all patients post-contrast images were also evaluated for degree and pattern of enhancement. RESULTS: Malignant lesions enhanced much more intensely than benign lesions (P<0.0005). Lack of enhancement was seen only in benign lesions. A heterogeneous pattern of enhancement was more frequently seen in malignancy (P<0.05). Additional information was provided on Gd-enhanced T1W images in 36% of cases compared to unenhanced T1 and T2W images. Diagnostic confidence was improved in 29%. The Gd-enhanced images changed the diagnosis correctly in 5% and incorrectly in 1%. CONCLUSION: Post-contrast images clarified specific issues, better defined lesion extent and margins in a majority of cases, and gave additional useful information in selected cases.

Marked improvement of severe polyneuropathy associated with multifocal osteosclerotic myeloma following surgery, radiation, and chemotherapy.

We describe a patient with a 3 year history of progressive polyneuropathy that rendered him severely quadriparetic and bedridden. Work up revealed an IgG lambda monoclonal spike and multifocal osteosclerotic myeloma. Remarkable improvement followed combined treatment with surgical excision, radiation therapy, and chemotherapy using chlorambucil, danazol, and hydrocortisone. Hence, we believe that aggressive local therapy associated with systemic chemotherapy should be considered in severely affected patients with multifocal osteosclerotic myeloma and peripheral neuropathy.

Use of gadolinium chelates in MR imaging of the spine.

Spinal disease can be divided into intramedullary, extramedullary-intradural, and extradural compartments. In the cord (intramedullary compartment), gadolinium chelates are useful to diagnose primary and metastatic tumors, inflammation, and demyelination, and to evaluate syringomyelia when a Chiari I malformation is not present. In the extramedullary-intradural compartment, gadolinium chelates are useful for the diagnosis of drop metastases, meningiomas, and schwannomas. In the extradural compartment, gadolinium chelates are most useful to distinguish recurrent disc herniation from epidural fibrosis in the postoperative back and may be useful to diagnosis the soft tissue component of osseous metastases.

Painful vasculitic neuropathy in HIV-1 infection: relief of pain with prednisone therapy.

Painful distal sensory polyneuropathy (DSP) is the most common peripheral neuropathy in patients with human immunodeficiency virus-1 (HIV-1) infection. There is no specific therapy for DSP, and nonspecific treatment with pain blockers and narcotic agents generally fails to adequately control the symptoms. We report two patients who had subacute painful neuropathy in the B2 (formerly AIDS-related complex [ARC]) stage of HIV-1 infection. Neurophysiologic studies revealed predominantly axonal sensorimotor neuropathy. Sural nerve biopsy in both cases showed a necrotizing vasculitis. Treatment with corticosteroids resulted in rapid relief of pain, followed by arrest of the neuropathic process. Although not previously emphasized, vasculitic neuropathy must be considered among the treatable causes of painful sensory neuropathy in HIV-1-infected individuals.