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.

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

PURPOSE: The 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. METHODS AND MATERIALS: Twenty-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. RESULTS: A 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. CONCLUSION: Changes 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.

Clinical application of PET for the evaluation of brain tumors.

The combination of FDG and PET has demonstrated clinical utility in the evaluation of patients with brain tumors. At the time of diagnosis, FDG PET provides information concerning the degree of malignancy and patient prognosis. After therapy, FDG PET is able to assess persistence of tumor, determine degree of malignancy, monitor progression, differentiate recurrence from necrosis, and assess prognosis. Other studies using PET provide information that may be clinically useful. Determination of tumor blood flow and permeability of the blood-brain barrier may help in the selection of appropriate therapy. Amino acid imaging using 11C-methionine is being evaluated in patients with brain tumors and provides different information than FDG imaging.

Utilization of lung scans by clinicians.

To determine the effect of clinical assessments and lung scan results on the management of patients, we studied 566 consecutive patients referred for lung scans because of suspected pulmonary embolism. Prior to the lung scan, the clinician was asked to estimate the probability of pulmonary embolus. Two or three days later the physician was contacted to determine how the patient was managed. The results of the lung scan strongly influenced patient management. Patients with high probability lung scans were treated for pulmonary embolism regardless of the clinical pretest estimate. Low and intermediate probability lung scans resulted in most patients not being treated for pulmonary embolism and not referred for pulmonary angiography. Only 55 of the 566 patients were referred for pulmonary angiography, and approximately one-half of these patients had lung scans with an intermediate probability for pulmonary embolism.

Ventilation-perfusion scintigraphy in the PIOPED study. Part I. Data collection and tabulation.

The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study of more than 700 patients is the largest existing study of the accuracy of lung scintigraphy in the diagnosis of acute pulmonary embolism. Perfusion scans were obtained in all patients and ventilation scans in almost all, using standardized techniques. Chest radiographs were obtained in all patients within 12 hr of the lung scan. Most patients underwent pulmonary arteriography. The images were interpreted according to a set of interpretive criteria which remained constant throughout the trial. A standardized, detailed description of each image set was derived by consensus of teams of two readers blinded to clinical and arteriographic findings. This communication reports the methods used to describe and categorize the ventilation-perfusion scintigrams obtained in patients who were enrolled in the PIOPED study. Scintigraphic technique is reviewed briefly, probability assessment is described and the scan description is reviewed in detail. The form used to describe the findings on ventilation-perfusion scans is reproduced. Use of this standardized description permits retrospective evaluation of the PIOPED interpretive criteria. In addition, it represents a rigorous approach to scan analysis which could facilitate application of formal interpretive schemes and enhance the reproducibility of lung scan interpretations in the clinical setting.

Ventilation-perfusion scintigraphy in the PIOPED study. Part II. Evaluation of the scintigraphic criteria and interpretations.

This article presents an evaluation of the criteria used for categorical interpretation of the ventilation-perfusion (V/Q) scans performed in the PIOPED study. In addition, the correlation of percent probability estimates with the actual frequency of pulmonary embolism (PE) is presented. Cases which met the PIOPED criteria for various diagnostic categories were selected by computerized search of the detailed scan descriptions that had been done as part of the study. The process by which the scans were described was detailed in Part I of this report. Most of the criteria appropriately categorized V/Q scans which satisfied them. However, we recommend that three criteria should be reconsidered: 1. A single moderate perfusion defect is appropriately categorized as intermediate, rather than as low probability. 2. Extensive matched V/Q abnormalities are appropriate for low probability, provided that the chest radiograph is clear. On the other hand, single-matched defects may be better categorized as intermediate probability. Although due to the small number of cases with this finding, no definite, statistically founded recommendation can be made. 3. Two segmental mismatches may not be the optimum threshold for high probability, and in some cases should be considered for intermediate probability. However, due to the small number of cases with this finding, no definite, statistically founded recommendation can be made. We suggest that the revised criteria resulting from these adjustments should now be used for the interpretation of V/Q scans.

Monitoring of neoadjuvant therapy response of soft-tissue and musculoskeletal sarcoma using fluorine-18-FDG PET.

UNLABELLED: The purpose of this study was to investigate the potential role of FDG-PET in the monitoring of neoadjuvant therapy of soft-tissue and musculoskeletal sarcomas. METHODS: Nine patients were studied. Neoadjuvant therapy consisted of either chemotherapy or combined radiotherapy and hyperthermia. The FDG-PET studies were obtained, when possible, prior to therapy, 1-3 wk after commencement of therapy, and prior to surgery after completion of neoadjuvant therapy. In two patients, all three studies were completed. The remainder of patients underwent one or two studies at varying timepoints. RESULTS: In tumors treated with combined radiotherapy and hyperthermia, well-defined regions of absent uptake developed within responsive tumors, correlating pathologically with necrosis. Following treatment, a peripheral rim of FDG accumulation was found to correlate pathologically with the formation of a fibrous pseudocapsule. In tumors treated with chemotherapy, FDG accumulation decreased more homogeneously throughout the tumor, in responsive cases. Despite 100% tumor cell kill in some patients, persistent tumor FDG uptake was observed which correlated pathologically with uptake within benign therapy-related fibrous tissue. Significant FDG accumulation was also observed at the site of an uncontaminated incisional biopsy. CONCLUSION: These initial results demonstrate changes in tumor accumulation of FDG during and after neoadjuvant therapy; these changes are dependent on the type of neoadjuvant therapy administered. Prominent FDG accumulation was observed in benign tissues both within and adjacent to the treated tumor.

Intact systolic left ventricular function in clinical congestive heart failure.

Clinical congestive heart failure (CHF) is traditionally associated wtih significant left ventricular (LV) systolic dysfunction. Over a 1-year period, 58 patients with CHF and intact systolic function (LV ejection fraction [EF] 62 +/- 11%) were identified. An objective clinical-radiographic CHF score was used to document the clinical impression. Based on radionuclide evaluation of peak filling rate, 38% of these patients were found to have a significant abnormality in diastolic function as measured by peak filling rate (less than 2.50 end-diastolic volume/s). An additional 24% of the patients had probable diastolic dysfunction with borderline abnormal peak filling rate measurements (2.5 to 3.0 end-diastolic volume/s). The disease states most frequently associated with CHF and intact systolic function were coronary artery disease and systemic hypertension. During a 3-month sampling period 42% of patients with clinical diagnosis of CHF referred to the nuclear cardiology laboratory were found to have intact systolic function; thus, intact systolic function is not uncommon in patients with clinical CHF. Abnormal diastolic function is the most frequently encountered mechanism for the occurrence of CHF. Definition of systolic and diastolic function appears relevant for development of optimal therapeutic strategies for the treatment of patients with CHF.

Detection of platelet deposition at the site of peripheral balloon angioplasty using indium-111 platelet scintigraphy.

Restenosis after balloon angioplasty may be mediated through platelet deposition at the site of arterial dilatation. The purpose of this study was to determine whether platelet deposition at the site of dilatation could be detected using indium-111 platelet scintigraphy. Fifteen patients, aged 60 +/- 9 years, with iliac or femoral (n = 12), renal artery (n = 2) or distal aortic (n = 1) stenoses were studied. All patients received intravenous heparin at the time of dilatation. Labeled platelets containing 471 +/- 65 muCi indium-111 were injected 0.25 to 4 hours after dilatation and 1 to 24 hours after imaging. In 11 of 12 patients with iliac and femoral dilatations, focal uptake was demonstrated at the angioplasty site. In 4 patients (2 patients with renal, 1 patient with iliofemoral, and 1 with distal aortic stenoses), uptake at the dilatation sites was not detected. This preliminary study indicates that despite intravenous heparin, platelets accumulate at sites of balloon dilatation. Platelet scintigraphy may be useful in predicting sites of future narrowing after angioplasty and may be used to test the efficacy of antiplatelet therapy in retarding restenosis.

Current status of ventilation-perfusion imaging.

The major clinical use of ventilation-perfusion (V/Q) scintigraphy is for the diagnosis of pulmonary embolism (PE). Accurate diagnosis of PE is essential since effective treatment is available but involves some risk to the patient. The scintigraphic characteristics of PE are segmental perfusion defects in lung that is normally ventilated and normal on the radiograph. The inherent shortcoming of perfusion scintigraphy is its lack of specificity. Combining a ventilation study with perfusion imaging improves the diagnostic specificity of lung scintigraphy. Xenon-133 is currently the most commonly used radionuclide for routine ventilation studies; a long washout technique is more sensitive than single-breath imaging when this radionuclide is used. We obtain preperfusion xenon-133 ventilation studies with a 4-min rebreathing equilibrium phase and a long 5-min washout phase to obtain maximum information. It is imperative that V/Q studies be interpreted with a current high quality chest radiograph. Interpretation of V/Q studies for PE is perhaps best done by assigning a probability diagnosis, since rarely is absolute specificity possible. This article details the criteria we use for these probability determinations.

Detection of deep venous thrombosis by magnetic resonance imaging.

OBJECTIVE: To determine the accuracy of gradient recalled echo magnetic resonance imaging in assessing deep venous thrombosis. DESIGN: This is a retrospective review of a prospective clinical experience in 216 consecutive patients studied using gradient recalled echo magnetic resonance imaging. Sixteen patients were unavailable for follow-up and 1 study was technically suboptimal, leaving 199 studies as the basis of this report. RESULTS: In 79 cases with confirmatory venography (n = 54), ultrasound (n = 16, thigh veins only), or computed tomography (n = 9, pelvic veins only), magnetic resonance imaging was 97 percent sensitive, 95 percent specific, and 96 percent accurate. Including cases that were normal by magnetic resonance imaging, not anticoagulated, and with uneventful follow-up as true normal cases, the corresponding sensitivity, specificity, and accuracy of magnetic resonance imaging were as follows: 97 percent, 98 percent, and 97 percent. CONCLUSION: Magnetic resonance imaging, using gradient recalled echo acquisitions, is capable of accurately diagnosing acute deep venous thrombosis.

Radioisotope labeled platelets in medical diagnosis.

The myriad of applications of indium-111 labeled platelets (111In-P), both in biomedical research and clinical diagnostic imaging, in recent years is an index of the potential of this technology. Because many diseases involve the vascular system, a nontoxic platelet label suitable for imaging has immense potential for diagnosis. Presently confined to research centers, this technique is currently used in three main diagnostic situations: deep vein thrombosis, cardiac thrombi, and organ (renal) transplantation rejection. Future applications will proliferate when difficulties in achieving rapid labeling are overcome, and the period between study initiation and final diagnosis is diminished. This review emphasizes current clinical applications and the potential role of this technology in diagnostic imaging.

Thoracic metastases from cervical carcinoma: current status.

Thoracic metastases from squamous carcinoma and adenocarcinoma of the cervix were studied by reviewing 245 consecutive cases to describe comparative incidence, natural history, and radiographic patterns. The incidence of chest metastases was higher for adenocarcinoma (20%) than for squamous carcinoma (4%). Few patients diagnosed in the early stages of squamous carcinoma developed metastases; for adenocarcinoma, chest metastases occurred regardless of the stage at diagnosis. For both histologies, parenchymal (often cavitary) nodules only were seen; lymphangitic pattern was not observed. Both adenopathy and malignant effusion are common (44% of metastases) in thoracic metastasis from squamous carcinoma. Adenopathy but not effusion was common in adenocarcinoma.

Contrast and accuracy of relaxation time measurements in acquired and synthesized multislice magnetic resonance images.

The effects of interslice spacing, the number of data points and other factors on the accuracy of relaxation time measurements and contrast have been investigated for both acquired and synthesized multislice MR images using experiments and computer simulations. The cross-excitation between adjacent slices in multislice imaging affects both contrast and derived relaxation times. Such measurements also are affected by the T1 and T2 of the materials imaged, the pulse sequence timing parameters, and the number of data points used to estimate the relaxation times. Errors in T1 and T2 may be severe, particularly for slice spacings less than 0.5 slice thickness and for long T1 and T2 materials. Consequently, the difference in signal intensities between two materials with different relaxation times also varies with slice spacing and between acquired and synthetic images, particularly for strongly T1-weighed images.

Effects of cell membrane disruption on the relaxation rates of blood and clot with various methemoglobin concentrations.

The magnetic resonance imaging (MRI) characteristics of hemorrhage and clotted blood change with age. The effects of methemoglobin and cell membrane lysis, factors which in part may underlie this evolution of imaging characteristics, were studied using clotted and heparinized dog blood at various methemoglobin concentrations. Cell lysis did not alter the longitudinal relaxation rate (1/T1) in clotted or unclotted samples. Membrane lysis altered significantly the transverse relaxation rate (1/T2) in both clotted and unclotted samples. Lysed samples of oxygenated blood at 0% methemoglobin had significantly higher T2 values than intact samples. At 0% methemoglobin, clotted samples had slightly but significantly shorter relaxation times than unclotted samples. Within the samples studied, large changes in the state of oxygenation and methemoglobin content were observed in less than 24 h. Such changes necessitate frequent monitoring of these parameters if serial studies are to be done.

Coumadin and 111In-labeled platelet uptake on experimental thrombi in dogs. Preliminary observations.

The effect of coumadin treatment upon the uptake of 111In platelets (111In-P) in dogs by experimental jugular thrombi and intravascular catheters was studied. Coumadin, in doses sufficient to raise the PT to the "therapeutic" range, did not impair scintigraphic visualization of thrombi on images obtained 4 hours after 111In-P injection. In addition, there was no obvious effect upon postmortem measurements of thrombus:blood or catheter:blood 111In activity ratios, consistent with the imaging data. However, slight delay in 111In-P accumulation on thrombi and catheters appeared to be present in dogs treated with coumadin, based on images obtained at 1, 2, and 3 hours after 111In-P injection. It is unlikely that coumadin's effect upon 111In-P uptake by thrombi would be significant in a clinical setting, although further studies would be required to confirm this.

Thick-section, single breath-hold magnetic resonance pulmonary angiography.

RATIONALE AND OBJECTIVES: Approaches to performing magnetic resonance angiography (MRA) of the pulmonary vasculature are described using very fast (repetition time [TR] less than 13 mseconds) radiofrequency (rf)-spoiled, gradient-recalled pulse sequences and the standard quadrature body imaging coil of a commercial 1.5-T MR imaging system. METHODS AND RESULTS: Signal-to-noise (SNR) is improved by signal averaging (Nex greater than or equal to 4) in a two-dimensional, single thick-section approach and by volume acquisition (Nex = 1) in a three-dimensional approach. Blood signal loss is minimized by using short, asymmetric echoes (echo time [TE] less than or equal to 2.7 mseconds). Respiratory motion is eliminated by keeping the scan time short enough (approximately 15 seconds) for image acquisition within a single breath-hold. Cardiac motion artifacts are reduced with section orientations that avoid intersecting the heart and/or use of small flip angle (alpha less than or equal to 25 degrees). CONCLUSIONS: Images of healthy volunteers showed that while single thick sections have superior SNR, the three-dimensional approach appears to produce better visualization of the peripheral vascular segments and offers improved ability to process the images to remove overlapping structures.

Localization of the conduction delay occurring during coronary arteriography.

The effect of coronary arteriography on intraventricular conduction was studied in 12 atropinized, open-chest dogs. Left bundle-branch (LB) and cavitary (V) potentials were recorded from a bipolar electrode catheter positioned against the septum below the aortic valve. Subendocardial (SEE) and subepicardial (IME) bipolar potentials were obtained from distal and proximal poles of multipolar electrode needles. Conduction times from LB to V, LB or V to SEE and SEE to IME were obtained during control and during Renografin 76 (REN) and normal saline injections into the left and right coronary arteries. Significant QRS axis changes and increased QRS duration occurred in 6 of 12 dogs simultaneously with LB-SEE and V-SEE delay. In 6 without axis changes, REN produced significant delay and increased QRS duration. Only REN to LCA produced significant changes. Coronary arteriography alters conduction through the distal left ventricular Purkinje system without affecting transmural conduction.

Renal magnetic resonance angiography in the preoperative detection of supernumerary renal arteries in potential kidney donors.

RATIONALE AND OBJECTIVES: Careful evaluation of the renovascular anatomy in potential living-related kidney donors is essential regarding the presence of accessory renal arteries. Conventional arteriography remains the standard of evidence for delineating the renal arterial supply. We assessed the utility of two-dimensional phase contrast (PC) magnetic resonance angiography (MRA) in the workup of potential living-related renal donors. METHODS: Thirty-nine patients were examined with conventional arteriography and MRA, which was performed on a 1.5-T system using a two-dimensional PC technique in both coronal and axial planes (repetition time[TR]/echo time [TE] = 39/8.5 msec; flip 60 degrees; matrix 256 x 128; field of view, 28 cm2; 2 excitations; first-order gradient-moment nulling; 7-mm section with 2-mm overlap). The number of hilar and polar supernumerary renal arteries was determined. Hilar supernumerary arteries were classified as co-dominant if they were similar in size to the ipsilateral main renal artery. RESULTS: Conventional arteriography identified 78 dominant and 13 supernumerary (3 co-dominant, 10 accessory) renal arteries. Magnetic resonance angiography identified the proximal 35 mm of all 78 dominant and the 3 co-dominant renal arteries. Of the remaining ten (7 polar and 3 hilar) accessory vessels, only four were correctly identified with MRA. CONCLUSION: The high error rate (60%) suggests that two-dimensional PC MRA, as implemented, should not be used in the preoperative evaluation of potential renal donors.

Clot-blood contrast in fast gradient-echo magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Contrast between clot and blood in magnetic resonance imaging (MRI) at 1.5T using fast gradient-echo pulse sequences (fast GRE), with 8 ms < TR < 20 mseconds was studied both in vitro and in clinical human deep venous thrombosis (DVT) to assess whether good contrast could be obtained at such short repetition times and at clinically relevant flow rates. METHODS: In vitro studies used an apparatus that contained flowing MnCl2[aq] (water adjusted with manganese chloride to have T1, T2 similar to blood) and an immobilized clot (T1, T2 similar to those in DVT) for flow velocities between 0 and 16.5 cm/sec. Seven patients with DVT were imaged with the fast GRE sequences to observe the clot-blood contrast in vivo. RESULTS: Peak contrast-to-noise ratio (CNR) was achieved using flip angles between 20 degrees and 40 degrees (increasing with flow velocity) with or without radiofrequency "spoiling," consistent with a natural spoiling effect of flow. The CNR between MnCI2[aq] and clot decreased less than 10% as TR was reduced 56% from 18 mseconds to 8 mseconds (30 degrees flip angle). In four patients with nonocclusive DVT, fast GRE imaging provided good contrast while in occlusive cases (three patients) the contrast was not as good as conventional GRE sequences with longer TR values (TR = 33 mseconds). CONCLUSION: A fast GRE sequence with TR = 8 mseconds, TE = 3 mseconds, and a flip angle = 40 degrees is a promising approach to speeding up the detection of nonocclusive clinical DVT.