Needle biopsy DNA ploidy status predicts grade shifting in prostate cancer.

DNA ploidy analysis of prostate needle biopsy specimens was performed to determine whether ploidy status could predict tumor grade shifting at radical prostatectomy. The paired needle biopsy and radical prostatectomy specimens from 111 randomly selected men with prostate cancer were obtained from the surgical pathology files of the Albany Medical Center Hospital. The original tumor grades were assigned by a staff of 12 surgical pathologists according to the Gleason system. Tumors with original Gleason scores < or = 6 were classified as low grade, and tumors with scores of > or = 7 were considered high grade. DNA ploidy analysis was performed on the needle biopsy specimens using the CAS 200 image analyzer (Becton Dickinson Immunocytometry Systems, Mountain View, CA, USA) on Feulgen stained 5-microm tissue sections. There were 88 diploid and 23 nondiploid cases. Thirty-eight of 111 (34%) of cases had grade shifting from needle biopsy to radical prostatectomy specimens. Of 89 low-grade needle biopsy cases, 28 (31%) were upgraded at radical prostatectomy. Of 22 high-grade needle biopsy cases, 10 (45%) were downgraded to low grade at radical prostatectomy. Of the 28 low-grade needle biopsy specimens that were upgraded at radical prostatectomy, 19 (68%) featured an aneuploid histogram and 9 (32%) were diploid. Nineteen of 28 (68%) of aneuploid low-grade tumors on needle biopsy became high-grade at radical prostatectomy. Nine of 10 (90%) diploid high-grade tumors at needle biopsy became low-grade at radical prostatectomy. Of the 38 cases in which ploidy and grade were incongruous, 28 (74%) had grade shifting. In a multivariate regression analysis, a high-grade Gleason score on radical prostatectomy specimens correlated significantly with needle biopsy ploidy (p = 0.0001) but not with needle biopsy grade (p = 0.15). The sensitivity of the needle biopsy grade in the detection of high-grade tumors on radical prostatectomy was 30%, and the specificity was 86%. The sensitivity of ploidy status in the prediction of high grade at radical prostatectomy was 78%, and the specificity was 96%. With a prostate-specific antigen (PSA) level of >0.4 ng/ml as the indicator of post-radical prostatectomy disease recurrence on a subset of 106 patients, on univariate analysis, disease recurrence was predicted by needle biopsy ploidy (p = 0.001) and radical prostatectomy grade (p = 0.04) but not by needle biopsy grade (p = 0.39). On multivariate analysis, needle biopsy DNA ploidy status independently predicted disease recurrence (p = 0.002), whereas needle biopsy and prostatectomy grade did not. These results indicate that DNA ploidy analysis of needle biopsy specimens of prostate cancer predicts grade shifting, that it is a more sensitive and specific indicator of final tumor grade at radical prostatectomy than is the original needle biopsy grade, and that ploidy status independently predicts postoperative disease recurrence.

Magnetic resonance chemical shift imaging and spectroscopy of atherosclerotic plaque.

An in vivo magnetic resonance imaging (MRI) technique for identification and characterization of atherosclerotic plaque was assessed in animal and human models. Atherosclerosis was induced in the abdominal aorta of four rabbits by a combination of balloon denudation and a high cholesterol diet. In vivo conventional spin-echo and fat/water suppressed images of the rabbit aortae were obtained at 1.5 T. Chemical shift imaging (CSI) was achieved using a hybridization of selective excitation and modified Dixon techniques. These techniques were then used to obtain images of atherosclerotic lesions in the carotid arteries of four patients prior to endarterectomy. The MRI results were corroborated by histologic and high-resolution proton MR spectroscopic (8.5 T) analysis of rabbit aorta, human carotid endarterectomy, and six additional human superficial femoral and iliac atherectomy specimens. All animal and human lesions were classified as either fatty streaks or fibrotic plaque. When compared to conventional spin-echo images, fat suppression by CSI substantially improved the measured contrast-to-noise ratio between plaque and vessel lumen, and enhanced its discrimination from periadventitial fat. In contrast, water suppression eliminated visualization of plaque due to the negligible amount of isotropic (liquid-like) signal from the immobilized lesion lipids. Magnetic resonance spectroscopy corroborated the CSI results by demonstrating broad, ill-defined fat resonances characteristic of nonmobile lipids in both human and rabbit atherosclerotic lesions. These findings indicate that in vivo MRI of plaque is technically feasible and can be markedly improved using chemical shift imaging.

Characterization of benign and malignant tissues of the thyroid gland. An ultrasonic approach using RF waveform analysis and pattern recognition.

A physical basis was developed for an accurate noninvasive technique to differentiate malignant thyroid tumors from benign lesions based upon a frequency-dependent attenuation model. The research effort utilized RF waveform analysis via a minicomputer based digital processing system. Data collection was performed using a standard clinical B-Mode diagnostic instrument with a transducer specially designed for imaging the thyroid gland. Differences between the frequency spectra of the RF waveforms for benign and malignant pathologies could be demonstrated in accordance with the proposed model.

Fatty liver. Chemical shift phase-difference and suppression magnetic resonance imaging techniques in animals, phantoms, and humans.

In vitro animal and human models were used to evaluate the potential of chemical shift magnetic resonance imaging (MRI) for assessing fatty liver. Phantoms of varying fat content were created from mayonnaise-agar preparations. Fatty liver was induced in eight rats by feeding them ethanol for three to six weeks (36% of total calories), whereas eight control rats were fed a normal diet. T1-weighted in-phase and opposed-phase MR images were obtained of the phantoms animals, and 28 human subjects. Additional images obtained in animals included long TR images with in-phase and opposed-phase technique, and hybrid chemical shift water and fat suppression. The rats were killed and histologic status was graded blindly by a hepatopathologist as normal, mild, moderate, or severe fatty change, for correlation with MR grading. Quantitative analysis of MR images included fat signal fraction for animals, and relative signal decrease between in-phase and opposed-phase images for phantom and human data. Phantom in-phase signal increased linearly with respect to fat content, whereas opposed-phase signal decreased linearly. MRI and histologic grading of rat livers were highly correlated, especially when based on water suppression images (r = 0.91, P = .0001). Opposed-phase images were also highly correlated, while fat suppression images were less effective. There was no overlap between MR-derived fat fractions for control (2.6%-5.7%) versus ethanol-fed rats (7.7%-17.9%, P = .0002). Human liver considered to be fatty by visual inspection (n = 8) had higher relative signal decrease than nonfatty liver (n = 22) (P less than .001). Phantom, animal, and human data demonstrate that comparison of T1-weighted in-phase and opposed-phase images is both practical and sensitive in the detection and grading of fatty liver.

Quantitative immunohistochemical determination of cathepsin D levels in prostatic carcinoma biopsies. Correlation with tumor grade, stage, PSA level, and DNA ploidy status.

National screening programs resulting in an increased detection rate of prostatic adenocarcinoma have prompted the search for new methods of predicting disease outcome that can be applied to the initial narrow bore needle biopsy specimens. Cathepsin D, a lysosomal aspartyl protease and autocrine mitogen, has been studied in a wide variety of human neoplasms as an invasion and metastasis marker. Prostatic carcinoma needle biopsy tumor cell cathepsin D content was measured in 61 men using a semiquantitative image analysis assisted immunohistochemical procedure. Results were compared with preoperative serum prostatic specific antigen levels, tumor grade, DNA ploidy status, pathologic stage after radical prostatectomy and disease recurrence during a median 2.6 year follow-up. Biopsy cathepsin D levels significantly correlated with tumor grade (P = .022) and DNA ploidy status (P = .028) by logistic regression analysis. Post-prostatectomy pathologic stage and disease recurrence did not correlate with tumor cathepsin D levels. Final prostatectomy grade and DNA ploidy status independently predicted metastasis and post-operative disease recurrence (P < .001). Although this study did not find independent prognostic status for cathepsin D in prostate cancer, the correlation with tumor grade and DNA ploidy status is noteworthy and the inter-relationship of outcome variables may prove of interest and warrant further evaluation of this potential predictor or CO-predictor of disease outcome.

Ultrasonography: an alternative to x-ray-guided needle localization of nonpalpable breast masses.

Preoperative ultrasonography was used as an alternative to x-ray mammography to localize 92 breast lesions encountered in 82 patients. Recommendation for biopsy was made on the basis of the ultrasonographic finding of a nonpalpable mass or an area of architectural distortion, or in the presence of equivocal physical findings if sonomammography demonstrated a solid or an anechoic mass. Sonomammography was performed in the operating room, just before anticipated biopsy, with a hand-held high-resolution scanner. When the suspicious area was imaged and its precise location noted, the breast was then prepared and draped in the usual manner, and a biopsy was performed. If the suspicious area could not be easily localized after the incision was made and the breast explored, the transducer was "gowned" and used directly in the wound to help find the lesion. This technique has proven effective and accurate. In selected patients ultrasonography may be used as well as, or instead of, x-ray needle localization for the precise excision of nonpalpable breast lesions, excluding calcifications.

Ureteral ectopia presenting as epididymitis and infertility.

A thirty-two-year-old man presented with a history of infertility, recurrent epididymitis, and a fluctuant pelvic mass on rectal examination. Preoperative evaluation disclosed a nonvisualized right kidney and a multiloculated cystic lesion in the pelvis. The intravenous pyelogram suggested a ureterocele on the right side. A cystic pelvic mass was noted on ultrasound and computed tomography. A dysplastic right kidney with an ectopic ureter inserting into a cystic seminal vesicle was found at surgical exploration.

Ultrasonography of the lower genitourinary tract.

As techniques and equipment become even more sophisticated, the use of diagnostic ultra-sound should expand. More accurate diagnoses, simplification of invasive techniques, and increased benefit of therapeutic techniques can be expected.

Ultrasound examination of the hand and foot.

The use of ultrasound in the examination of the distal extremities is a recent application of sonography of the musculotendinous system. Real-time sonography is unique in providing a dynamic study of complex anatomic structures such as the flexor tendons of the hand. The normal anatomic appearance of the hand and foot are reviewed as well as the sonographic appearance of pathologic conditions of the distal extremities.

Ultrasound examination of tendons.

This article reviews the type of equipment used in sonography of the tendons, the method of approach in viewing normal tendon anatomy, and the sonographic appearance in pathologic conditions of the tendons. The role of ultrasound in follow-up studies is also emphasized because of its noninvasive nature.

Recent advances in magnetic resonance imaging of the knee.

The examination of the knee has rapidly become the most important non-neurologic application of MR imaging. The widespread availability of high signal-to-noise knee coils has made routine imaging with T2-weighted sequences in both coronal and sagittal planes possible in 30 minutes. The spin-echo sequence remains the most important imaging technique, although many newer sequences have also been applied to the knee, with varying degrees of success. Important pitfalls in diagnosis, such as high signal intensity in the posterior horn of the medial meniscus and the transverse meniscal ligament, displaced buckethandle meniscal tears, and discoid menisci, can be recognized with experience. Common clinical problems that are encountered include meniscal cysts, osteonecrosis, and bone bruises. Detection of subtle injuries of the medial collateral ligament, patellar tendon, and anterior cruciate ligament requires careful observation. Intra-articular loose bodies can be reliably detected with MR imaging, and it should be recognized that localized pigmented villonodular synovitis can sometimes simulate the appearance of a loose body. MR imaging is a valuable noninvasive procedure that is complementary to arthroscopy in the evaluation of diseases of the knee.

Magnetic resonance imaging of prostate cancer: update.

Prostate cancer is the most common cancer in the world, the most frequently diagnosed in the United States, and the second most lethal cancer in U.S. men. Earlier diagnosis implies better prognosis. However, prognosis may be dependent upon the stage of the malignancy at the time of diagnosis and implementation of appropriate therapy. Clinical staging, even with the development of serum prostate-specific antigen and other studies, has not proven to be highly accurate, particularly to identify and quantitate local disease and extension. Imaging has, in the past, also had limited success. With the development of computed tomography (CT), endorectal ultrasound, and magnetic resonance imaging (MRI), there was great expectations for improvement. However, CT and ultrasound have not been as accurate as hoped. MRI, because of its multiorientation and multiparameter abilities, has been the most definitive imaging tool for staging of local extension, yet still has limitations. The prostate capsule, the neurovascular bundles, the seminal vesicle, and other regions prone to initial attack by cancer extension can be seen exquisitely clearly by the newer approaches to MRI. Cancer extension, however, cannot be consistently identified when it is microscopic. MRI is an accurate identifier of macroscopic, even subtle macroscopic disease, but there are still limitations in its ability to diagnose all pathology.

Magnetic resonance imaging of the prostate and bladder.

Prostate carcinoma is the most common cancer in men and the second most lethal malignancy among the American male population. Nevertheless, it is potentially curable if detected early and treated appropriately. Treatment options vary depending on the extent (stage) of the cancer. MRI has no role as a screening method for prostatic carcinoma because it is expensive, time consuming, and unable to differentiate benign from malignant disease, but it can detect early prostatic cancers in patients with known tumor and can accurately stage these tumors. MRI is becoming the imaging modality of choice for local staging of prostate cancer and is rapidly replacing CT and ultrasonography for this purpose. Treatment protocols for bladder carcinoma also depend on the stage of the tumor. Clinical staging of bladder cancer has been limited. MRI is as good as or better than CT in bladder tumor staging when extravesical tumor involvement is present. MRI also has the potential to become useful in determining the depth of wall invasion in tumors confined to the bladder.

Multiple spin-echo MR imaging of the body: image contrast and motion-induced artifact.

For a given TR and TE, image quality changes when the number of spin echoes obtained is varied. To investigate the importance of this in clinical imaging, a total of 4 patients and 9 volunteers had MRI examinations of the abdomen (n = 7) and/or pelvis (n = 8) which included at least 2 sequences with identical TR (2000 or 2500 ms), TE (80 ms) and other parameters, but with a different series of refocusing pulses. Sequences included single-echo (S), asymmetric and symmetric double-echo (AD and SD) and quadruple-echo (Q) techniques. Image contrast and severity of motion-induced artifact was measured via blind examination by 3 independent MRI radiologists and calculation of signal-difference, signal-difference-to-noise ratios and intensity of motion-induced "ghost artifact." The order of decreasing signal differences was S, SD, AD and Q, and all of three liver lesions were better seen with S than with SD techniques. These observations are consistent with signal loss from cumulative inaccuracies from multiple 180 degrees RF pulses. The order of increasing intensity of ghost artifact was Q, SD, AD and S, consistent with the beneficial motion artifact-reducing effects of even-echo rephasing. Knowledge of these effects of multi-echo imaging allows one to make informed decisions about imaging protocols rather than to simply obtain multiple echoes "because they are free."

Partial angle inversion recovery (PAIR) MR imaging: spin-echo and snapshot implementation.

The effects of varying the inversion or excitation RF pulse flip angles on image contrast and imaging time have been investigated in IR imaging theoretically, with phantoms and with normal volunteers. Signal intensity in an IR pulse sequence as a function of excitation, inversion and refocusing pulse flip angles was calculated from the solution to the Bloch equations and was utilized to determine the contrast behavior of a lesion/liver model. Theoretical and experimental results were consistent with each other. With the TI chosen to suppress the fat signal, optimization of the excitation pulse flip angle results in an increase in lesion/liver contrast or allows reduction in imaging time which, in turn, can be traded for an increased number of averages. This, in normal volunteers, improved spleen/liver contrast-to-noise ratio (9.0 vs. 5.7, n = 8, p less than 0.01) and suppressed respiratory ghosts by 33% (p less than 0.01). Reducing or increasing the inversion pulse from 180 degrees results in shorter TI needed to null the signal from the tissue of interest. Although this decreases the contrast-to-noise ratio, it can substantially increase the number of sections which can be imaged per given TR in conventional IR imaging or during breathold in the snapshot IR (turboFLASH) technique. Thus, the optimization of RF pulses is useful in obtaining faster IR images, increasing the contrast and/or increasing the number of imaging planes.

Bone marrow findings on magnetic resonance images of the knee: accentuation by fat suppression.

Long TR/double spin-echo magnetic resonance images of the knee were obtained with and without the use of fat suppression techniques in seven patients with high signal intramedullary lesions. Comparison between images was performed qualitatively and quantitatively. Contrast-to-noise ratios between focal defects and surrounding fatty marrow were higher with fat suppression in all cases. The mean contrast-to-noise ratio for images obtained with fat suppression was 53.6, while for images obtained without fat suppression the mean contrast-to-noise ratio was 17.3 (p less than 0.01).

MRI of aggressive fibromatosis: frequent appearance of high signal intensity on T2-weighted images.

Magnetic resonance imaging of seven patients with eight pathologically proven desmoid tumor tumors was performed and retrospectively reviewed. On T2-weighted images, all but one lesion demonstrated increased signal intensity relative to muscle, and had signal intensity similar to that of fat. The signal was heterogenous in six of these seven lesions. In a patient with synchronous multicentric lesions, light microscopy correlation revealed increased cellularity in one lesion with increased signal intensity and dense collagenous elements in a second lesion, with decreased signal intensity. High signal intensity appears to be typical but nonspecific, and in following these patients could indicate recurrent tumor, superimposed inflammatory process or granulation tissue.

Variable flip angle imaging and fat suppression in combined gradient and spin-echo (GREASE) techniques.

Conventional "proton density" and "T2-weighted" spin-echo images are susceptible to motion induced artifact, which is exacerbated by lipid signals. Gradient moment nulling can reduce motion artifact but lengthens the minimum TE, degrading the "proton density" contrast. We designed a pulse sequence capable of optimizing proton density and T2-weighted contrast while suppressing lipid signals and motion induced artifacts. Proton density weighting was obtained by rapid readout gradient reversal immediately after the excitation RF pulse, within a conventional spin-echo sequence. By analyzing the behavior of the macroscopic magnetization and optimizing excitation flip angle, we suppressed T1 contribution to the image, thereby enhancing proton density and T2-weighted contrast with a two- to four-fold reduction of repetition time. This permitted an increased number of averages to be used, reducing motion induced artifacts. Fat suppression in the presence of motion was investigated in two groups of 8 volunteers each by (i) modified Dixon technique, (ii) selective excitation, and (iii) hybrid of both. Elimination of fat signal by the first technique was relatively uniform across the field of view, but it did not fully suppress the ghosts originating from fat motion. Selective excitation, while sensitive to the main field inhomogeneity, largely eliminated the ghosts (0.21 +/- 0.05 vs. 0.29 +/- 0.06, p less than 0.01). The hybrid of both techniques combined with bandwidth optimization, however, showed the best results (0.17 +/- 0.04, p less than 0.001). Variable flip-angle imaging allows optimization of image contrast which, along with averaging and effective fat suppression, significantly improves gradient- and spin-echo imaging, particularly in the presence of motion.

Femoral head avascular necrosis in sickle cell anemia: MR characteristics.

Since considerable expansion of hematopoietic marrow occurs in patients with sickle cell anemia (SCA), magnetic resonance images of 20 hips in 10 patients with known homozygous SCA were reviewed to determine a) if low signal hematopoietic marrow extended into the femoral capital epiphysis and b) if the MR characteristics of avascular necrosis (AVN) differed depending on the type of epiphyseal marrow. Our results revealed variable epiphyseal marrow type; mixed (fatty and hematopoietic) marrow (42%), fatty marrow (32%), hematopoietic marrow (16%) and hemosiderotic marrow (10%). AVN occurred irrespective of the underlying marrow. Segmental areas of low signal intensity in variable shapes (ring, band, crescent or large homogeneous area) was the most consistent MR manifestation of AVN in SCA. A low signal intensity peripheral rim surrounding a central zone, isointense with epiphyseal marrow on T1 and T2 weighted images, was most frequently observed similar to that described in patients without hemoglobinopathy. The notable difference, however, was of segmental areas within the same femoral head that demonstrated variable central zone signal on T2 weighted images. Further, while an increase in hip joint fluid is commonly seen with both early and advanced AVN in patients without hemoglobinopathy; it was increased in only one hip in patients with SCA. The observed differences in MR characteristics may be due to different pathophysiology of AVN in patients with SCA.

Marrow infarction in sickle cell anemia: correlation with marrow type and distribution by MRI.

Ischemic necrosis of bone is believed to occur exclusively in areas of predominantly fatty marrow. Sickle cell disease is unusual in that marrow infarction occurs in areas of active hematopoiesis. MR images of long bone obtained in ten patients with sickle cell anemia (SCA) were analyzed to correlate the distribution and appearance of marrow infarction with the type of marrow. While the hematopoietic marrow predominated in metaphyseal and diaphyseal regions of femurs and tibias, the fatty or mixed marrow was the most common pattern in epiphyses. Infarcts occurred in fatty as well as hematopoietic marrow. Marrow infarcts were isointense or minimally hyperintense on T1 weighted images with the hematopoietic marrow and therefore difficult to detect. On T2 weighted images, the infarcts showed very high signal. T2 weighted images are essential for detection of marrow infarction. Soft tissue changes seen as low signal on T1 and high signal on T2, may be secondary to intramuscular injections of analgesics or muscle ischemia occurring during sickle crisis.