The past 25 years in medical imaging research: a memoir

During the past 25 years, medical imaging research has progressed in both scope and quality. Factors intrinsic to the specialty and changes occurring in medicine and society have fostered imaging research development. The advent of new, computer-based technologies that can be brought to bear on research, the increasing sophistication of researchers, and the greater availability of extramural funding have been primary factors in the promulgation of research improvements. Radiology researchers have the opportunity to play an important role in the genesis of the molecular medicine of the future. Whether they do so is dependent on whether radiologists identify necessary resources, new researchers receive appropriate training, and investigators are willing to think differently than they have in the past about the capabilities of imaging.     

Measurement of vocal fold collision forces during phonation: methods and preliminary data.

Forces applied to vocal fold tissue as the vocal folds collide may cause tissue injury that manifests as benign organic lesions. A novel method for measuring this quantity in humans in vivo uses a low-profile force sensor that extends along the length and depth of the glottis. Sensor design facilitates its placement and stabilization so that phonation can be initiated and maintained while it is in place, with minimal interference in vocal fold vibration. In 2 individuals with 1 vibrating vocal fold and 1 nonvibrating vocal fold, peak collision force correlates more strongly with voice intensity than pitch. Vocal fold collision forces in 1 individual with 2 vibrating vocal folds are of the same order of magnitude as in previous studies. Correlations among peak collision force, voice intensity, and pitch were indeterminate in this participant because of the small number of data points. Sensor modifications are proposed so that it can be used to reliably estimate collision force in individuals with 2 vibrating vocal folds and with changing vocal tract conformations.     

Behavioral disturbances in geropsychiatric inpatients across dementia types

The objective of this study was to compare differences in behavioral, psychiatric, and cognitive status among geropsychiatric inpatients with Alzheimer's, vascular, alcohol-induced, and mixed dementia. Participants included 150 patients with dementia consecutively admitted to an acute geropsychiatric inpatient unit. Measures included the Mini-Mental State Examination, Cohen-Mansfield Agitation Inventory, Cumulative Illness Rating Scale, Basic and Independent Activities of Daily Living, Positive and Negative Syndrome Scale for Schizophrenia, and the Initiation/Perseveration subscale of the Dementia Rating Scale. No significant differences existed in the character or severity of agitation among patients with Alzheimer's, vascular, alcohol-related and mixed dementia. Interestingly, patients with vascular dementia compared to patients with other dementias admitted for behavioral disturbances were less cognitively impaired and more medically burdened.     

Oim mice exhibit altered femur and incisor mineral composition and decreased bone mineral density

To investigate the role of the pro alpha 2(I) collagen chains of type I collagen in mineralization we used the oim (osteogenesis imperfecta model) mouse as our model system. The oim/oim mouse (homozygous for a null mutation in its COL1A2 gene of type I collagen) fails to synthesize functional pro alpha 2(I) collagen chains, synthesizing only homotrimers of pro alpha 1(I) collagen chains. To evaluate the role of pro alpha 2(I) collagen in type I collagen structure/function in mineralized tissues, we examined age-matched oim/oim, heterozygous (oim/+), and wild-type (+/+) mouse femurs and incisors for mineral composition (calcium, phosphorus, magnesium, fluoride, sodium, potassium, and chloride) by neutron activation analyses (NAA), and bone mineral content (BMC) and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) in a longitudinal study (7 weeks to 16 months of age). NAA demonstrated that oim/oim femurs had significant differences in magnesium, fluoride, and sodium content as compared with +/+ mouse femurs, and oim/oim teeth had significant differences in magnesium content as compared to +/+ teeth. The ratio of calcium to phosphate was also significantly reduced in the oim/oim mouse femurs (1.58 +/- 0.01) compared with +/+ femurs (1.63 +/- 0.01). DEXA demonstrated that oim/oim mice had significantly reduced BMC and BMD as compared to oim/+ and +/+ mice. Serum and urine calcium, magnesium, and phosphorus levels, and Ca(47) absorption across the gut were equivalent in oim/oim and +/+ mice, with no evidence of hypercalciuria. These studies suggest that the known decreased biomechanical properties of oim/oim bone reflect both altered mineral composition as well as the decreased BMD, which further suggests that the presence of alpha2(I) chains plays an important role in mineralization.     

Population-based analysis of arteriovenous malformation treatment

OBJECT: The author sought to describe overall management data on cerebral arteriovenous malformations (AVMs) and to focus the actuarial need for different treatment modalities on a population-based scale. Such data would seem important in the planning of regional or national multimodality strategies for the treatment of AVMs. This analysis of a nonselected, consecutive series of patients representing every diagnosed case of cerebral AVM in a population of 1,000,000 over one decade may serve to shed some light on these treatment aspects. METHODS: During the 11-year period from 1989 to 1999, data from every patient harboring a cerebral AVM that was presented clinically or discovered incidentally in a strictly defined population of 986,000 people were collected prospectively. No patient was lost to follow up. There were 12.4 de novo diagnosed AVMs per 1,000,000 population per year (135 AVMs). Large high-grade AVMs (Spetzler-Martin classification) were rare, and Grade 1 to 3 lesions represented 85% of the caseload. Hemorrhage was the initial manifestation of AVM in 69.6% of the cases. lntracerebral hematoma was the most common hemorrhagic manifestation occurring in 78 patients. There were 4.4 cases per 1,000,000 population per year of hematomas needing expedient surgical evacuation. In the remaining patients who did not require hematoma surgery, small, critically located Grade 3 and Grade 4 lesions amounted to 1.6 cases per 1,000,000 population per year. There were 5.8 cases per 1,000,000 population per year of Grade 1 to 2 and larger noncritically located Grade 3 malformations. There were 0.5 cases per 1,000,000 population per year of Grade 5 AVMs. The overall outcome in 135 patients was classified as good according to the Glasgow Outcome Scale (Score 5) in 61% of the cases, and the overall mortality rate was 9%. CONCLUSIONS: In centers with population-based referral, AVM of the brain is predominantly a disease related to intracranial bleeding. and parenchymal clots have a profound impact on overall management outcome. The rupture of an AVM is as devastating as that of an aneurysm. Aneurysm ruptures are more lethal, whereas AVM rupture tends to result in more neurological disability due to the high occurrence of lobar intracerebral hematoma. In an attempt to quantify the need for different modalities of AVM treatment based on a population of 1,000,000 people, figures for surgeries performed range from six to 10 operations per year and embolization as well as gamma knife surgery procedures range from two to seven per year, depending on the strategy at hand. When using nonsurgical approaches to Grade 1 to 3 lesions, the number of patients requiring treatment with more than one method for obliteration increases drastically as does the potential risk for procedure-related complications.     

Benzo[a]pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium

While tobacco smoke has been conclusively identified as a lung carcinogen, there is much debate over which smoke constituent(s) are primarily responsible for its carcinogenicity. Previous studies in our laboratory suggested that highly lipophilic carcinogens are slowly absorbed in the thicker epithelium of the conducting airways, potentially allowing for substantial local metabolism. The bioactivation of polycyclic aromatic hydrocarbons in airway epithelium may, hence, be important in tobacco smoke-induced carcinogenesis. In the present study, the hypothesis of slow absorption and substantial local metabolic activation of highly lipophilic carcinogen in airway epithelium was tested in dogs. A single dose of tritiated benzo[a]pyrene (BaP) dissolved in a saline/phospholipid suspension was instilled in the trachea, just anterior to the carina. At intervals of a few minutes up to 30 min over a 3-h period, blood samples were drawn from the azygous vein, which drains the area around the point of instillation, and from the systemic circulation. Tissue samples were taken at the end of the experiment. The concentration of BaP with depth into the tracheal mucosa was determined with autoradiography. BaP was slowly absorbed into the trachea with a half-time of approximately 73 min, which is consistent with diffusion-limited passage through the epithelium and lead to local doses in the tracheal epithelium that were more than a 1000-fold those of other tissues. The long retention of BaP in the epithelium provided the local metabolizing enzymes with high substrate levels over a long period, resulting in extensive metabolism. At 3 h after the exposure, 23% of the BaP-equivalent activity remained in the tracheal mucosa. Of this fraction, 13% was parent compound, 28% was organic extractable, 31% was water-soluble, and 28-7% of the instilled dose was bound to tracheal tissues. These results explain the tendency of highly lipophilic carcinogens, such as BaP, to induce tumors at the site of entry and, furthermore, indicate that the highly lipophilic components of tobacco smoke and polluted air may be the most important contributors to lung tumors of the conducting airways.      

A phase II study of paclitaxel plus carboplatin as first-line chemotherapy for women with metastatic breast carcinoma

BACKGROUND: This Phase II multicenter study evaluated the efficacy and toxicity of paclitaxel (200 mg/m(2) by 3-hour infusion) with carboplatin (area under the curve 6 mg/mL per minute) administered every 3 weeks as first-line therapy for women with metastatic breast carcinoma. METHODS: Eligible patients had measurable metastatic disease and an Eastern Cooperative Oncology Group performance status of 0-2. Prior adjuvant chemotherapy, including anthracycline-based therapy, was allowed, as was prior hormonal therapy as part of either adjuvant treatment or treatment for metastasis. Prior therapy with taxanes or platinum was not allowed. RESULTS: A total of 53 patients were enrolled in this study, with 50 patients evaluable for response and toxicity. The overall response rate was 62% (95% confidence interval ?CI, 48-75%); 16% of patients had complete responses and 46% had partial responses. The median time to progression was 7.3 months (95% CI, 5.9-12.9), and the 12-month survival estimate was 72% (95% CI, 61-86%). Therapy was generally well tolerated. Grade 3-4 neutropenia was the predominant toxicity, observed in 82% of patients, but there were no episodes of febrile neutropenia or sepsis. Hematopoietic growth factors were not routinely necessary. Grade 3 peripheral neuropathy occurred in 16% of patients. CONCLUSIONS: Paclitaxel (200 mg/m(2)) with carboplatin (area under the curve 6 mg/mL per minute) demonstrated substantial efficacy in patients with metastatic breast carcinoma, and the 12-month survival rate of 72% was encouraging. This therapy represents a viable option for patients with metastatic disease.