H. Dirk Sostman

Cytotoxic drug-induced lung disease

Cytotoxic drugs, principally bleomycin, methotrexate and busulfan, have been associated with pulmonary toxicity. Cytotoxic drug-induced lung disease may be difficult to establish with certainty because other causes of pulmonary disease are frequently present. We discuss the clinical, roentgenographic and histologic effects of the administration of bleomycin, methotrexate, busulfan and other cytotoxic agents on the lungs and suggest that these agents may also cause pulmonary malignancies. We note the importance of careful patient monitoring and withdrawal of a demonstrated offending agent.

Very Low Probability Interpretation of V/Q Lung Scans in Combination with Low Probability Objective Clinical Assessment Reliably Excludes Pulmonary Embolism: Data from PIOPED II

Use of a very low probability interpretation of ventilation/perfusion (V/Q) lung scans, if verified by prospective evaluation to have a low positive predictive value (PPV), will reduce the number of nondiagnostic interpretations of V/Q scans and may be particularly useful in patients with a relative contraindication to CT. The purpose of this investigation was to test the hypothesis that a very low probability interpretation of the V/Q scan has a PPV of <10%. Methods: Data are from PIOPED II (Prospective Investigation of Pulmonary Embolism Diagnosis II). Very low probability criteria are (a) nonsegmental perfusion abnormalities, (b) perfusion defect smaller than corresponding radiographic lesion, (c) ≥2 matched V/Q defects with regionally normal chest radiograph, (d) 1–3 small segmental perfusion defects (<25% of a segment), (e) solitary triple matched defect in middle or upper lung zones, (f) stripe sign around the perfusion defect(s), and (g) perfusion defect from pleural effusion equal to one third or more of the pleural cavity with no other perfusion defect. Results: A very low probability consensus interpretation of the V/Q scan was made in 56% of patients. The PPV of a very low probability interpretation of the V/Q scans was 36 of 440 patients (8.2%). Among patients with suspected pulmonary embolism who had a low clinical probability objective clinical assessment and a very low probability V/Q scan, the PPV was 8 of 259 patients (3.1%). Among women ≤40 y, the PPV of the very low probability V/Q with a low objective clinical assessment was 1 of 50 (2%). Conclusion: The very low probability V/Q scan together with a low probability clinical assessment reliably excludes pulmonary embolism.

Therapy monitoring in human and canine soft tissue sarcomas using magnetic resonance imaging and spectroscopy

PURPOSEnThe goals of this study were to determine whether magnetic resonance parameters (a) can identify early during therapy those patients most likely to respond to hyperthermia and radiotherapy, (b) can provide prior to or early during therapy information about the temperature distributions which can be obtained in patients receiving hyperthermia, and (c) can provide an understanding of the effects of hyperthermia on tumor metabolic status.nnnMETHODS AND MATERIALSnTwenty-one human patients and 10 canine patients with soft tissue sarcomas treated with preoperative hyperthermia and radiation had a series of magnetic resonance imaging and phosphorous spectroscopy studies done. To address the goals for both the human and canine populations, changes in mean T2 relaxation times, pH, and various phosphometabolite ratios from the pretreatment (Study 1) to the post first hyperthermia study (Study 2) were correlated with treatment outcome; pretreatment magnetic resonance parameters and changes in magnetic resonance parameters (Study 2-Study 1) were compared with various cumulative thermal descriptors; and thermal descriptors of the first hyperthermia were compared with changes in magnetic resonance phosphometabolite ratios.nnnRESULTSnA decrease in adenosine triphosphate/phosphomonoester from study 1 to study 2 is associated with a greater chance of > or = 95% necrosis in surgical resected tumors from human patients, but no significant relationships were observed between changes in tumor pH or phosphometabolite ratios and time to local failure in dogs. Pretreatment magnetic resonance parameters correlated with various thermal dose descriptors in canines but not in humans. Change in adenosine triphosphate/inorganic phosphate and phosphomonoester signal to noise ratio correlated with cumulative thermal descriptors in dogs and humans, respectively. In dogs only, increases in thermal dose resulted in decreases in high energy phosphometabolites.nnnCONCLUSIONnChanges in magnetic resonance parameters early during therapy may be predictive of treatment outcome. Pretreatment and changes in magnetic resonance parameters appear to predict how well a tumor will be heated during hyperthermia. Magnetic resonance spectroscopy also appears to be a useful tool to study the effects of various thermal doses on tumor metabolic status.

The diagnostic accuracy/efficacy of MRI in differentiating hepatic hemangiomas from metastatic colorectal/breast carcinoma : A multiple reader ROC analysis using a jackknife technique

PURPOSEnOur purpose was to determine the diagnostic accuracy efficacy of a simple MR technique in differentiating hepatic hemangiomas from colorectal or breast metastases using a multiple reader method.nnnMETHODnThirty-seven cases with confirmed hepatic hemangiomas and 115 with confirmed hepatic metastases (colon primary, n = 86; breast primary, n = 29) evaluated with MRI at 1.5 T were retrospectively collected. A single lesion in a single slice from each patient was randomly selected; the images were masked and then were interpreted in random order by five separate readers blinded to the diagnosis using a five point diagnostic scale (from definite hemangioma to definite metastasis). Morphologic characteristics of lesion margin, signal intensity relative to other structures, and internal architecture (homogeneous versus heterogeneous) were also assessed independently of the five point diagnostic scale. Three of the readers had > 8 years of experience, while the other two had 1 and 3 years. The diagnostic scale results were subjected to receiver operating characteristic (ROC) analysis using a jackknife method. kappa-Statistics were applied to assess interreader agreement in the morphologic characteristics. A logistic regression model was used to determine which characteristics predicted pathology and reader diagnosis.nnnRESULTSnROC analysis showed the average area under the curve over all readers was (0.91 (0.89-0.93 95% confidence interval) (p < 0.0001). An analysis of variance showed no significant difference between the areas under the curves of each reader (p = 0.6433). When the definite and probable categories for hemangioma and metastasis were combined, the sensitivity/specificity for the diagnosis of hemangioma ranged from 57 to 73%/91 to 97%. The positive/negative predictive value ranged from 72 to 84%/87 to 91%. For the morphologic assessment, there was significant agreement between the readers (p < 0.0001-0.0037). A sharp margin and lesion signal equal to or greater than CSF predicted the presence of a hemangioma (p = 0.0148 and p < 0.0001, respectively). A sharp margin, lesion signal equal to or greater than CSF, and a homogeneous internal architecture all predicted the reader diagnosis of definitely or probably hemangioma.nnnCONCLUSIONnFor multiple readers, T2-weighted SE MRI alone is a very specific method for distinguishing hemangiomas from metastatic colon or breast carcinoma. Morphologic characteristics of a sharp margin and a high signal predict the presence of a hemangioma. Last, reader experience does not appear to have a significant effect on the specificity.

Fast spoiled gradient-recalled MR imaging of thoracic aortic dissection: Preliminary clinical experience at 1.5 T

The purpose of this study was to evaluate fast spoiled gradient-recalled (FSPGR) magnetic resonance (MR) imaging in the diagnosis of thoracic aortic dissection (TAD). Twenty-eight patients with suspected TAD underwent MR imaging with FSPGR and either cine or cardiac-gated spin-echo MR techniques. The average scanning time for the FSPGR images was approximately 1 min. Three readers interpreted the FSPGR images for the presence or absence of TAD. An ROC analysis was done. At a specificity of 90%, the sensitivity ranged from 52% to 90% for the three readers. Pulsatility artifacts and mural thrombus were causes of false-positive and false-negative readings. The areas under the ROC curves (Az) ranged from 0.85 to 0.97 for the three readers. There was a statistically significant difference in the Az values for two of the experienced readers (p = .02). The correct type of dissection was determined in only 65% of the true-positive diagnoses. FSPGR has a very limited role in screening and for rapid evaluation of the unstable patient. The results are reader dependent and susceptible to pulsatility artifacts. Determination of the type of dissection is limited. With a suspected thoracic aortic dissection, therefore, additional imaging sequences should be obtained to maximize accuracy.

Proton-decoupled phosphorus-31 magnetic resonance spectroscopy in the evaluation of native and well-functioning transplanted kidneys

RATIONALE AND OBJECTIVESnTo evaluate whether decoupling improves signal-to-noise ratio and frequency resolution of in vivo kidney spectra, and to compare native and well-functioning transplant kidneys.nnnMETHODSnProton decoupling in conjunction with three-dimensional chemical shift imaging (3D-CSI) in phosphorus-31 magnetic resonance (MR) spectroscopy was used with a spatial resolution of 64 cm3 and 17-minute acquisition time to compare native (n = 10) and well-functioning transplant (n = 9) kidneys.nnnRESULTSnProton decoupling improved peak amplitudes by almost 30%, as well as chemical shift resolution of in vivo kidney spectra. No statistically significant differences in phosphometabolite ratios and renal spectra were observed between healthy volunteers and patients with nonrejecting transplants. The phosphodiester-phosphomonoester ratio was 3.02 +/- 0.88, phosphomonoester-inorganic phosphate ratio was 1.07 +/- 0.44, and inorganic phosphate-adenosine triphosphate ratio was 0.58 +/- 0.22 after correction for saturation effects.nnnCONCLUSIONnImproved spectra of native and transplant kidneys can be obtained in vivo with MR spectroscopy by using a short acquisition time.

Pitfalls in myocardial perfusion assessment with dynamic MR imaging after administration of a contrast material bolus in dogs

RATIONALE AND OBJECTIVESnThe authors evaluated the artifacts observed on myocardial perfusion curves derived from an inversion-prepared fast gradient-echo (GRE) imaging sequence in dogs after injection of a gadolinium-based contrast agent.nnnMATERIALS AND METHODSnSix mongrel dogs were divided into three groups. In groups 1 and 2, anesthesia was maintained with pentobarbital. Group 2 also received an intravenous injection of atropine (0.03 mg/kg). In group 3, anesthesia was maintained with isoflurane (1.0%). Imaging was performed on a 1.5-T magnetic resonance (MR) imaging unit (one section per heart beat, a 30 x 15-cm field of view, 10-mm section thickness, and 64-kHz bandwidth). Region-of-interest (ROI) markers were placed on the blood pool of the left intraventricular cavity, anterior wall of the left ventricle, and anterior to the chest wall to track respiratory motion.nnnRESULTSnIn group 1, the signal intensity (SI) periodically increased during each inspiration due to respiratory sinus arrhythmia. The relation between the SI increase and the variation of the delay between images was demonstrated in vitro and by computer simulations. No periodic increase of the SI was observed when regular cardiac rhythm was maintained by pharmacologic inhibition of the vagal-mediated chronotropic response with either the addition of atropine to pentobarbital or the use of isoflurane as the anesthetic agent.nnnCONCLUSIONnIn an inversion-prepared fast GRE sequence, respiratory sinus arrhythmia can induce periodic SI increase by varying the respiratory rate interval and delay between images.

Errors in the assessment of the efficacy of MRI pulse sequences

The effects of the echo delay TE on contrast in saturation recovery MRI have been analyzed both theoretically and with experimental brain scans. It is demonstrated that the influence of the TE values offered as minimal values by all major current equipment manufacturers is not insignificant, but produces a degree of T2 weighting that considerably degrades the useful contrast that could be obtained from T1 weighted studies. Consequently, conclusions drawn about the relative performances of T1 and T2 weighted sequences may be incorrect if based on saturation recovery images obtained with inappropriate echo times.

MR imaging of experimental and clinical thrombi at 1.5 T

We have previously reported that the T1 and T2 of experimental clots at 0.47 T varies considerably depending upon the method used in their preparation. However, these studies, while relevant to midfield imaging, may not reflect accurately the behavior of such thrombi at higher field strengths. Accordingly, we studied the T1 and T2 at 1.5 T of experimental thrombi prepared by several methods and compared these results with the relaxation times of clinical deep venous thrombi measured in situ in patients. The relationship between the T2 values for the different clot preparation methods was different at 1.5 T than at 0.47 T. The combined use of thrombin and epsilon-amino caproic acid produced thrombi with T1 and T2 indistinguishable from clinical deep venous thrombi.

Assessment of Intracellular Oxygenation of Solid Tumors

This study was launched to determine whether oxygenation of tumor cells, as opposed to intra-tumor red blood cells, could be verified with a non-invasive methodology. The markers used to differentiate between the two cell types were hemoglobin for the RBC and cytochrome c oxidase (cytochrome aa3) for the tumor cells. Near infrared and visible mu lt iwave length, differential spectrophotometry were used to directly assess in vivo kinetic changes in relative hemoglobin saturation, tissue blood volume, and cytochrome aa3 redox state in the BA1112 rhabdomyosarcoma and in skeletal muscle, its derivative tissue. Tissue hemodynamics and intracellular redox status were monitored both independently in tumors and concurrently with muscle in anesthetized WAG/Rij/Y rats breathing normoxic, hyperoxic, hypoxic, and hypercapnic gas mixtures and also in response to administered vasoactive agents. Optical signal responses were not necessarily influenced by changes in arterial perfusion pressure (MAP) as verified by use of vasoactive agents chosen to increase and decrease MAP. Hypoxia and hypercapnic acidosis invariably decreased both tumor and muscle oxygenation as evidenced by hemoglobin deoxygenation, reduced tissue blood volume, and increased intra-mitochondrial cyt aa3 reduction. Muscle was not responsive to hyperoxia (FIO2=1.0). In tumors, hyperoxia consistently increased the HbFIO2 content even though tissue blood volume fell. However, the direction and magnitude of oxidation-reduction changes in cytochrome aa3 varied among tumors. These responses were not correlated with the size (volume) of the tumor. We speculate that the underlying cause of this idiosyncratic behavior was the variable stage and degree of vascular proliferation/degeneration in the tumors. These findings emphasize that increased oxygenation of the tumor cells, for instance prior to radiation treatment, can only be judged by their intracellular cytochrome response, not by the local blood oxygenation.